霉菌毒素DON、ZEA及其联合染毒对体外培养鸡脾脏淋巴细胞凋亡的分子机制研究
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摘要
脱氧雪腐镰刀菌烯醇(deoxynivalenol, DON)、玉米赤霉烯酮(zearalenone, ZEA)是饲料中两种最常见的霉菌毒素。霉菌毒素不仅降低饲料营养价值,导致动物生长性能、繁殖性能下降,而且最重要和最本质的危害是破坏机体免疫系统造成免疫抑制,引起疾病高发。脾脏是霉菌毒素作用于免疫系统的主要靶器官,霉菌毒素可导致脾脏淋巴细胞凋亡,进而使机体免疫功能降低。本研究以原代培养鸡脾脏淋巴细胞为模型,研究DON、ZEA单独或联合染毒对鸡脾脏淋巴细胞的凋亡损伤效应及其机理,为进一步阐明DON、ZEA及其联合免疫毒性作用的机理提供理论依据。
应用CCK-8法测定了染DON、ZEA后48h对鸡脾脏淋巴细胞的半数抑制浓度(IC5o)为30.82±10.48μg/mL和23.91±4.96μg/mL,表明DON、ZEA均能够影响鸡脾脏淋巴细胞的增殖活性。在此基础上设计DON单独染毒剂量水平为0.2μg/mL0.8μg/mL、3.2μg/mL、12.5μg/mL、50μg/mL,ZEA单独染毒剂量水平为O.lμg/mL、0.4μg/mL、1.6μg/mL、6.25μg/mL、25μg/mL,DON和ZEA联合染毒剂量为0.0125μg/mL和0.00625μg/mL、0.05μg/mL和0.025μg/mL、0.2μg/mL和0.1μg/mL、0.8μg/mL和0.4μg/mL,分别进行DON、ZEA单独或联合染毒48h对鸡脾脏淋巴细胞的毒性效应：①鸡脏脾脏淋巴细胞凋亡率、坏死率、乳酸脱氢酶释放率、DNA损伤及凋亡形态学的变化；②鸡脾脏淋巴细胞胞内SOD、CAT、GSH-Px活性及GSH、MDA含量；③鸡脾脏淋巴细胞膜ATP酶(Ca-ATPase、Na/K-ATPase)活性、胞内pH、线粒体膜电位、活性氧、钙离子水平及其钙调蛋白(CaM)的mRNA的表达；④鸡脾脏淋巴细胞的相关凋亡基因(bcl-2、Bax、Bak-1、p53及Caspase-3等)mRNA表达(实时荧光定量PCR)及细胞培养液上清中相关的凋亡基因蛋白含量(ELISA法)。
DON、ZEA及其联合染毒48h：①各染毒组细胞凋亡率、坏死率、乳酸脱氢酶活性均显著或极显著高于对照组(P<0.05或0.01),随毒素剂量增加,三个指标均明显升高,呈量效依赖效应,且联合染毒组各项指标均大于相应剂量单独染毒组。各染毒组脾脏淋巴细胞DNA出现片段化条带,随毒素浓度增加,DNA片段化条带越明显；细胞表现出核皱缩、呈新月形、染色质致密浓染、核碎裂等典型凋亡特征；细胞凋亡率明显大于坏死率。②与对照组比较,除DON、ZEA单独染毒最低剂量组个别指标外,染毒组SOD、CAT、GSH-Px活性和GSH含量均显著或极显著降低(P<0.05或P<0.01),随毒素剂量的增加,指标均明显降低；联合染毒组4个指标均小于相应剂量单独染毒组。而MDA含量随毒素浓度升高而升高,除DON单独染毒最低剂量组、联合染毒最低剂量组与对照组差异不显著,其余各组与对照组差异极显著((P<0.01)；联合染毒组MDA均大于相应剂量单独染毒组。③各染毒组细胞内活性氧(ROS)、钙离子水平、CaM mRNA表达水平均随毒素剂量的升高而增加,显著或极显著高于对照组(P<0.05或0.01),联合染毒组除DZ3组(DON0.2μg/mL+ZEA0.1μg/mL) CaM mRNA表达水平大于ZEA0.1μg/mL组而小于DON0.2μg/mL组外,其余均大于相应剂量单独染毒组。线粒体膜电位水平、胞内pH、Ca2+-ATPase与Na+/K+-ATPase活性,均随毒素剂量的升高而降低,显著或极显著低于对照组(P<0.05或0.01)；联合染毒组均小于相应剂量单独染毒组。④各染毒组随毒素剂量升高,细胞内p53、BAX、Bak-1及Caspase-3的mRNA表达升高,低剂量组与对照组差异不显著外,均显著或极显著高于对照组(P<0.05或P<0.01),且Bax mRNA表达水平与Bcl-2mRNA表达水平的比值亦升高,显著或极显著高于对照组(P<0.05或0.01)；联合染毒DZ4组(DON0.8μg/mL+ZEA0.4μg/mL) p53mRNA表达大于DON0.8μg/mL组而小于ZEA0.4μg/mL组,DZ3组(DON0.2μg/mL+ZEA0.1μg/mL) Bak-1mRNA表达均小于ZEA0.1μg/mL组和DON0.2μg/mL组；其余联合染毒组均高于相应剂量单独染毒组。各染毒组随毒素浓度升高,细胞培养上清液中p53、BAX、Bak-1及Caspase-3的含量升高,均显著或极显著高于对照组(P<0.05或0.01),联合染毒组均高于相应剂量单独染毒组；而bcl-2含量却下降,极显著低于对照组(P<0.01),联合染毒组均低于相应剂量单独染毒组。
结论：①DON或ZEA单独染毒及其联合染毒对鸡脾脏淋巴细胞损伤、DNA片段化及细胞凋亡呈浓度依赖性,联合染毒呈亚加性协同效应；在试验设计的DON、ZEA浓度下,脾脏淋巴细胞凋亡性死亡在细胞损伤过程中发挥主导作用。②DON、ZEA导致细胞内抗氧化酶活性降低、氧化产物增加导致鸡脾脏淋巴细胞氧化损伤是细胞凋亡性死亡的重要机制。③DON或ZEA单独染毒及其联合染毒导致鸡脾脏淋巴细胞线粒体膜电位降低,细胞内酸化,离子平衡失调等一系列细胞内环境稳态失衡促进了细胞凋亡。④DON或ZEA单独染毒及其联合染毒上调Bcl-2基因家族基因(Bax、 Bak-1)、抑制Bcl-2基因家族基因中bcl-2基因表达；上调p53基因和Caspase-3基因表达,激活p53和Caspase通路而诱导细胞凋亡增加；两毒素联合表现出亚加性效应。
Deoxynivalenol (DON) and zearalenone (ZEA) are the most common mycotoxins in the feed. The mycotoxins can not only reduce the nutritional value of feed, but also inhibit the growth performance and the reproductive performance of animal. Moreover, the mycotoxins can destroy the immune system in animal and induce immunosuppression, which causes high incidence of diseases. The main target organ of mycotoxins in immune system is the spleen. The mycotoxins can cause the apoptosis of the splenic lymphocyte, and inhibit the body immune function. In this study, the toxic effects of DON and/or ZEA on the splenic lymphocytes of chicken were investigated in vitro, which will offer some theoretic evidences for further exploring the mechanism in immunotoxicity of DON and/or ZEA.
By CCK-8test, the IC50of DON and ZEA to chicken splenic lymphocytes in vitro at48h were30.82±10.48μg/mL and23.91±4.96μg/mL, individually. So, it s howed that DON or ZEA affected cell proliferation activity. On this basis of IC50, the final concentrations of DON were0.2,0.8,3.2,12.5, and50μg/mL; and the fi nal concentrations of ZEA were0.1,0.4,1.6,6.25, and25μg/mL, individually. The exposure doses of DON and ZEA joint were DON0.0125μg/mL and ZEAO.00625μ g/mL, DON0.05μg/mL and ZEA0.025μg/mL, DON0.2μg/mL and ZEAO.1μg/mL, DO N0.8μg/mL and ZEA0.4μg/mL, individually. Then, the toxic effects of different dos es of DON or/and ZEA on chicken splenic lymphocytes in vitro for48h were inve stigated. The determination indicators are as follows:①Effects of DON or/and ZEA on the apoptotic rates, necrotic rates, LDH release, DNA damage, and apoptotic of morphological changes in chicken splenic lymphocytes;②Activities of SOD, CAT, GSH-Px, and contents of GSH, MDA in chicken splenic lymphocytes;③Act ivities of Ca2+-ATPase and Na+/K+-ATPase, intracellular pH, levels of mitoch ondrial membrane potential(Δφ), reactive oxygen species (ROS), intracellular [C a2+]i), and CaM relative mRNA level in chicken splenic lymphocytes;④Apoptotic genes (bcl-2and Bax bak-1, p53and caspase-3, etc.) relative mRNA1evel in chicken splenic lymphocytes(real-time PCR) and the concentrations of related apoptosis gene protein in supernatants of chicken splenic lymphocytes (ELISA).
The results were as followed:①The apoptotic rates, necrotic rates, LDH release in these exposed groups were significantly higher than those in the control group (P<0.05or0.01). These indicators were significantly increased, and showed a dose-dependent effect following toxin dose increasing. Also, these indicators by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose. Following toxin dose increasing, DNA fragmentations in all exposed groups were more obvious than that of the control group. Typical morphological changes of apoptosis in the DON and/or ZEA groups, were nuclear shrinkage, drop-like structure of nuclear, dense nuclear chromatin, nuclear fragment. The apoptotic rates were significantly greater than the necrosis rates.②Compared with the control group, the activities of SOD, CAT, GSH-Px and GSH levels in the exposed groups decreased significantly (P<0.05or P<0.01), except for these of the low-dose groups (DON or ZEA). Following toxin dose increasing, these indicators were significantly decreased. Also, these indicators induced by the combinations of DON and ZEA, were always lower than those in the related DON or ZEA group in the same exposure dose. But following toxin dose increasing, the concentrations of MDA were increased. Compared with the control group, the concentrations of MDA increased significantly (P<0.01) except for the low-dose groups (DON and/or ZEA). Also, the concentrations of MDA induces by combinations of DON and ZEA, were always higher than those in the related DON or ZEA group in the same exposure dose.③Following toxin dose increasing, compared to the control group, intracellular ROS,[Ca2+]i, and CaM relative mRNA level increased significantly (P<0.05or0.01). Also, these indicators induced by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose, except that CaM relative mRNA level of DZ-3group (DON0.2μg/mL+ZEA0.1p.g/mL) was higher than that of Z1group (ZEA0.1μg/mL), but was lower than that of Dl group (DON0.2μg/mL). The mitochondrial Aφ, intracellular pH, activities of Ca2+-ATPase and Na+-/K+-ATPase decreased significantly (P<0.05or0.01) following toxin dose increasing. These indicators induced by combinations of DON and ZEA were always lower than those in the related DON or ZEA group in the same exposure dose.④Following toxin dose increasing, p53, Bax, Bak-1, and Caspase-3relative mRNA levels in the exposed groups increased significantly (P<0.05or0.01), except for the low-dose groups (DON and/or ZEA). And the ratio of Bax/Bcl-2in the exposed groups was significantly higher than that of the control group (P<0.05or0.01). These indicators induced by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose, except that p53relative mRNA level of DZ-4group (DON0.8μg/mL+ZEA0.4ug/mL) was higher than that of D2group(DON0.8μg/mL), but was lower than that of Z2group (ZEA0.4ug/mL), Bak-1relative mRNA level of DZ-3group (DON0.2μg/mL+ZEA0.1μg/mL) was lower than that of D1group(DON0.2μg/mL) and Z1group (ZEA0.1μg/mL). Following toxin dose increasing, the concentrations of p53of Bax, and Bak-1and Caspase-3in supernatants of chicken splenic lymphocytes gradually increased in a dose-dependent manner. There were significant differences between the exposed groups and the control group (P<0.05or0.01). Also these indicators induced by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose. But the concentrations of Bcl-2significantly decreased compared to the control (P<0.01), and these indicators of combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose.
Based on these results, the conclusions are as follow:①DON and/or ZEA exposure induced chiken splenic lymphocytes damage, DNA damage, and apoptosis in a dose-dependent manner, and synergistic effect lies in the administration of DON combined with ZEA. The apoptotic mechanism played a chief role in the cellular death induced by DON and/or ZEA at these doses in present study.②DON and/or ZEA exposure inhibited the activities of the anti-oxidative enzymes, which leaded to the increased oxidation products. Further, the oxidative damage in the chicken splenic lymphocytes was enhanced. The oxidative damage could be the first mechanism of apoptotic in the chicken splenic lymphocytes induced by DON and/or ZEA.③DON and/or ZEA exposure induced depletion of mitochondrial Aφ, disorder of intracellular homeostasis, i.e. intracellular acidification, and ion imbalance. The imbalance of the intracellular environment might be the second mechanism of apoptotic in the chicken splenic lymphocytes induced by DON and/or ZEA.④For Bcl-2family genes, DON and/or ZEA exposure induced increased the expression of Bax gene and the expression of Bak-1gene, but decreased expression of Bcl-2gene. Besides, DON and/or ZEA exposure also increased the expression of p53gene and the expression of Caspase-3gene, then p53and Caspase pathway was activated. The activated p53and Caspase pathway might be the third mechanism of apoptotic in the chicken splenic lymphocytes induced by DON and/or ZEA. In a word, there was an obvious synergistic effect of DON combined with ZEA on the cellular damage in the chicken splenic lymphocytes
应用CCK-8法测定了染DON、ZEA后48h对鸡脾脏淋巴细胞的半数抑制浓度(IC5o)为30.82±10.48μg/mL和23.91±4.96μg/mL,表明DON、ZEA均能够影响鸡脾脏淋巴细胞的增殖活性。在此基础上设计DON单独染毒剂量水平为0.2μg/mL0.8μg/mL、3.2μg/mL、12.5μg/mL、50μg/mL,ZEA单独染毒剂量水平为O.lμg/mL、0.4μg/mL、1.6μg/mL、6.25μg/mL、25μg/mL,DON和ZEA联合染毒剂量为0.0125μg/mL和0.00625μg/mL、0.05μg/mL和0.025μg/mL、0.2μg/mL和0.1μg/mL、0.8μg/mL和0.4μg/mL,分别进行DON、ZEA单独或联合染毒48h对鸡脾脏淋巴细胞的毒性效应：①鸡脏脾脏淋巴细胞凋亡率、坏死率、乳酸脱氢酶释放率、DNA损伤及凋亡形态学的变化；②鸡脾脏淋巴细胞胞内SOD、CAT、GSH-Px活性及GSH、MDA含量；③鸡脾脏淋巴细胞膜ATP酶(Ca-ATPase、Na/K-ATPase)活性、胞内pH、线粒体膜电位、活性氧、钙离子水平及其钙调蛋白(CaM)的mRNA的表达；④鸡脾脏淋巴细胞的相关凋亡基因(bcl-2、Bax、Bak-1、p53及Caspase-3等)mRNA表达(实时荧光定量PCR)及细胞培养液上清中相关的凋亡基因蛋白含量(ELISA法)。
DON、ZEA及其联合染毒48h：①各染毒组细胞凋亡率、坏死率、乳酸脱氢酶活性均显著或极显著高于对照组(P<0.05或0.01),随毒素剂量增加,三个指标均明显升高,呈量效依赖效应,且联合染毒组各项指标均大于相应剂量单独染毒组。各染毒组脾脏淋巴细胞DNA出现片段化条带,随毒素浓度增加,DNA片段化条带越明显；细胞表现出核皱缩、呈新月形、染色质致密浓染、核碎裂等典型凋亡特征；细胞凋亡率明显大于坏死率。②与对照组比较,除DON、ZEA单独染毒最低剂量组个别指标外,染毒组SOD、CAT、GSH-Px活性和GSH含量均显著或极显著降低(P<0.05或P<0.01),随毒素剂量的增加,指标均明显降低；联合染毒组4个指标均小于相应剂量单独染毒组。而MDA含量随毒素浓度升高而升高,除DON单独染毒最低剂量组、联合染毒最低剂量组与对照组差异不显著,其余各组与对照组差异极显著((P<0.01)；联合染毒组MDA均大于相应剂量单独染毒组。③各染毒组细胞内活性氧(ROS)、钙离子水平、CaM mRNA表达水平均随毒素剂量的升高而增加,显著或极显著高于对照组(P<0.05或0.01),联合染毒组除DZ3组(DON0.2μg/mL+ZEA0.1μg/mL) CaM mRNA表达水平大于ZEA0.1μg/mL组而小于DON0.2μg/mL组外,其余均大于相应剂量单独染毒组。线粒体膜电位水平、胞内pH、Ca2+-ATPase与Na+/K+-ATPase活性,均随毒素剂量的升高而降低,显著或极显著低于对照组(P<0.05或0.01)；联合染毒组均小于相应剂量单独染毒组。④各染毒组随毒素剂量升高,细胞内p53、BAX、Bak-1及Caspase-3的mRNA表达升高,低剂量组与对照组差异不显著外,均显著或极显著高于对照组(P<0.05或P<0.01),且Bax mRNA表达水平与Bcl-2mRNA表达水平的比值亦升高,显著或极显著高于对照组(P<0.05或0.01)；联合染毒DZ4组(DON0.8μg/mL+ZEA0.4μg/mL) p53mRNA表达大于DON0.8μg/mL组而小于ZEA0.4μg/mL组,DZ3组(DON0.2μg/mL+ZEA0.1μg/mL) Bak-1mRNA表达均小于ZEA0.1μg/mL组和DON0.2μg/mL组；其余联合染毒组均高于相应剂量单独染毒组。各染毒组随毒素浓度升高,细胞培养上清液中p53、BAX、Bak-1及Caspase-3的含量升高,均显著或极显著高于对照组(P<0.05或0.01),联合染毒组均高于相应剂量单独染毒组；而bcl-2含量却下降,极显著低于对照组(P<0.01),联合染毒组均低于相应剂量单独染毒组。
结论：①DON或ZEA单独染毒及其联合染毒对鸡脾脏淋巴细胞损伤、DNA片段化及细胞凋亡呈浓度依赖性,联合染毒呈亚加性协同效应；在试验设计的DON、ZEA浓度下,脾脏淋巴细胞凋亡性死亡在细胞损伤过程中发挥主导作用。②DON、ZEA导致细胞内抗氧化酶活性降低、氧化产物增加导致鸡脾脏淋巴细胞氧化损伤是细胞凋亡性死亡的重要机制。③DON或ZEA单独染毒及其联合染毒导致鸡脾脏淋巴细胞线粒体膜电位降低,细胞内酸化,离子平衡失调等一系列细胞内环境稳态失衡促进了细胞凋亡。④DON或ZEA单独染毒及其联合染毒上调Bcl-2基因家族基因(Bax、 Bak-1)、抑制Bcl-2基因家族基因中bcl-2基因表达；上调p53基因和Caspase-3基因表达,激活p53和Caspase通路而诱导细胞凋亡增加；两毒素联合表现出亚加性效应。
Deoxynivalenol (DON) and zearalenone (ZEA) are the most common mycotoxins in the feed. The mycotoxins can not only reduce the nutritional value of feed, but also inhibit the growth performance and the reproductive performance of animal. Moreover, the mycotoxins can destroy the immune system in animal and induce immunosuppression, which causes high incidence of diseases. The main target organ of mycotoxins in immune system is the spleen. The mycotoxins can cause the apoptosis of the splenic lymphocyte, and inhibit the body immune function. In this study, the toxic effects of DON and/or ZEA on the splenic lymphocytes of chicken were investigated in vitro, which will offer some theoretic evidences for further exploring the mechanism in immunotoxicity of DON and/or ZEA.
By CCK-8test, the IC50of DON and ZEA to chicken splenic lymphocytes in vitro at48h were30.82±10.48μg/mL and23.91±4.96μg/mL, individually. So, it s howed that DON or ZEA affected cell proliferation activity. On this basis of IC50, the final concentrations of DON were0.2,0.8,3.2,12.5, and50μg/mL; and the fi nal concentrations of ZEA were0.1,0.4,1.6,6.25, and25μg/mL, individually. The exposure doses of DON and ZEA joint were DON0.0125μg/mL and ZEAO.00625μ g/mL, DON0.05μg/mL and ZEA0.025μg/mL, DON0.2μg/mL and ZEAO.1μg/mL, DO N0.8μg/mL and ZEA0.4μg/mL, individually. Then, the toxic effects of different dos es of DON or/and ZEA on chicken splenic lymphocytes in vitro for48h were inve stigated. The determination indicators are as follows:①Effects of DON or/and ZEA on the apoptotic rates, necrotic rates, LDH release, DNA damage, and apoptotic of morphological changes in chicken splenic lymphocytes;②Activities of SOD, CAT, GSH-Px, and contents of GSH, MDA in chicken splenic lymphocytes;③Act ivities of Ca2+-ATPase and Na+/K+-ATPase, intracellular pH, levels of mitoch ondrial membrane potential(Δφ), reactive oxygen species (ROS), intracellular [C a2+]i), and CaM relative mRNA level in chicken splenic lymphocytes;④Apoptotic genes (bcl-2and Bax bak-1, p53and caspase-3, etc.) relative mRNA1evel in chicken splenic lymphocytes(real-time PCR) and the concentrations of related apoptosis gene protein in supernatants of chicken splenic lymphocytes (ELISA).
The results were as followed:①The apoptotic rates, necrotic rates, LDH release in these exposed groups were significantly higher than those in the control group (P<0.05or0.01). These indicators were significantly increased, and showed a dose-dependent effect following toxin dose increasing. Also, these indicators by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose. Following toxin dose increasing, DNA fragmentations in all exposed groups were more obvious than that of the control group. Typical morphological changes of apoptosis in the DON and/or ZEA groups, were nuclear shrinkage, drop-like structure of nuclear, dense nuclear chromatin, nuclear fragment. The apoptotic rates were significantly greater than the necrosis rates.②Compared with the control group, the activities of SOD, CAT, GSH-Px and GSH levels in the exposed groups decreased significantly (P<0.05or P<0.01), except for these of the low-dose groups (DON or ZEA). Following toxin dose increasing, these indicators were significantly decreased. Also, these indicators induced by the combinations of DON and ZEA, were always lower than those in the related DON or ZEA group in the same exposure dose. But following toxin dose increasing, the concentrations of MDA were increased. Compared with the control group, the concentrations of MDA increased significantly (P<0.01) except for the low-dose groups (DON and/or ZEA). Also, the concentrations of MDA induces by combinations of DON and ZEA, were always higher than those in the related DON or ZEA group in the same exposure dose.③Following toxin dose increasing, compared to the control group, intracellular ROS,[Ca2+]i, and CaM relative mRNA level increased significantly (P<0.05or0.01). Also, these indicators induced by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose, except that CaM relative mRNA level of DZ-3group (DON0.2μg/mL+ZEA0.1p.g/mL) was higher than that of Z1group (ZEA0.1μg/mL), but was lower than that of Dl group (DON0.2μg/mL). The mitochondrial Aφ, intracellular pH, activities of Ca2+-ATPase and Na+-/K+-ATPase decreased significantly (P<0.05or0.01) following toxin dose increasing. These indicators induced by combinations of DON and ZEA were always lower than those in the related DON or ZEA group in the same exposure dose.④Following toxin dose increasing, p53, Bax, Bak-1, and Caspase-3relative mRNA levels in the exposed groups increased significantly (P<0.05or0.01), except for the low-dose groups (DON and/or ZEA). And the ratio of Bax/Bcl-2in the exposed groups was significantly higher than that of the control group (P<0.05or0.01). These indicators induced by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose, except that p53relative mRNA level of DZ-4group (DON0.8μg/mL+ZEA0.4ug/mL) was higher than that of D2group(DON0.8μg/mL), but was lower than that of Z2group (ZEA0.4ug/mL), Bak-1relative mRNA level of DZ-3group (DON0.2μg/mL+ZEA0.1μg/mL) was lower than that of D1group(DON0.2μg/mL) and Z1group (ZEA0.1μg/mL). Following toxin dose increasing, the concentrations of p53of Bax, and Bak-1and Caspase-3in supernatants of chicken splenic lymphocytes gradually increased in a dose-dependent manner. There were significant differences between the exposed groups and the control group (P<0.05or0.01). Also these indicators induced by combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose. But the concentrations of Bcl-2significantly decreased compared to the control (P<0.01), and these indicators of combinations of DON and ZEA were always higher than those in the related DON or ZEA group in the same exposure dose.
Based on these results, the conclusions are as follow:①DON and/or ZEA exposure induced chiken splenic lymphocytes damage, DNA damage, and apoptosis in a dose-dependent manner, and synergistic effect lies in the administration of DON combined with ZEA. The apoptotic mechanism played a chief role in the cellular death induced by DON and/or ZEA at these doses in present study.②DON and/or ZEA exposure inhibited the activities of the anti-oxidative enzymes, which leaded to the increased oxidation products. Further, the oxidative damage in the chicken splenic lymphocytes was enhanced. The oxidative damage could be the first mechanism of apoptotic in the chicken splenic lymphocytes induced by DON and/or ZEA.③DON and/or ZEA exposure induced depletion of mitochondrial Aφ, disorder of intracellular homeostasis, i.e. intracellular acidification, and ion imbalance. The imbalance of the intracellular environment might be the second mechanism of apoptotic in the chicken splenic lymphocytes induced by DON and/or ZEA.④For Bcl-2family genes, DON and/or ZEA exposure induced increased the expression of Bax gene and the expression of Bak-1gene, but decreased expression of Bcl-2gene. Besides, DON and/or ZEA exposure also increased the expression of p53gene and the expression of Caspase-3gene, then p53and Caspase pathway was activated. The activated p53and Caspase pathway might be the third mechanism of apoptotic in the chicken splenic lymphocytes induced by DON and/or ZEA. In a word, there was an obvious synergistic effect of DON combined with ZEA on the cellular damage in the chicken splenic lymphocytes
引文
[1]Palmgren M S, Lee L S. Separation of mycotoxin-containing sources in grain dust and determination of their mycotoxin potential[J]. Environ Health Perspect,1986,66:105-108.
[2]陈心仪,Rebekah, Rawlings亚洲地区饲料和畜禽养殖业霉菌毒素危害实况[J].饲料广角,2008,10：39-42.
[3]王若军,苗朝华.中国饲料及饲料原料受霉菌污染的调查报告[J].饲料工业,2003,24(7)：53-54.
[4]敖志刚,陈代文.2006-2007年中国饲料及饲料原料霉菌毒素污染调查报告[J].中国畜牧兽医,2008,35(1)：152-156.
[5]张丞,刘颖莉.2008年上半年中国饲料和原料中霉菌毒素污染调查报告[J].饲料研究,2008,11：57-59.
[6]张丞,刘颖莉.2009年上半年中国饲料和原料中霉菌毒素污染情况[J].中国畜牧杂志,2009,45(16)：46-48.
[7]Hsin Yi Chen, Rebekah Rawlings亚洲地区饲料原料和配合饲料中霉菌毒素水平的调查[J].饲料研究,2008,9：28-31.
[8]吴裕本,张健.家禽生产中霉菌毒素的现状及控制[J].中国家禽,2006,28(11)：43-44.
[9]李荣涛,谢刚,付鹏程,等.小麦和玉米中玉米赤霉烯酮污染情况初探(Ⅰ)[J].2004,32(5)：36-38.
[10]邓舜洲,何庆华,章英,等.竞争间接EIASA检测饲料中脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮[J].江西农业大学学报,2006,28(2)：289-292.
[11]杨晓飞.四川地区主要饲料霉菌毒素分布规律的研究[D].四川农业大学,2007.
[12]Rotter B A, Preluskey D B, Pestka, J J. Toxicology of deoxynivalenol(vomitoxin)[J]. Toxicol, 1996,48:1-34.
[13]Ronald D Plattner, Chris M Maraagos. Determination of Deoxynivalenol and Nivalenol in Corn and Wheat by Liquid Chromatography with Electrospray Mass Spectrometry[J]. Journal of Aoac International,2003,86(1):61-65.
[14]Pestka JJ, HR Zhor, Y Moon, et al. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes:untraveling a paradox [J]. Toxicol. Lett,2004,153:61 73.
[15]Yoshizawa T, N Morooka. Trichothecenes from mold-infected cereals in Japan. In J. V. Rodricks, C. W. Hesseltine, and M. A. Mehlmen (eds.), Mycotoxins in Human and Animal Health [J]. Pathotox Publishers, Inc., Park Forest,1977:309-321.
[16]吴永宁.现代食品安全科学[M].北京：化学工业出版社,2003：310-319.
[17]Yoshizawa T, Morooka N. Studies on the toxic substances in infected cereals:Acute toxicities of new trichothecene mycotoxins:deoxynivalenol and its monoacetate [J]. J Food Hyg Soc Jpn,1974, 15:261-269.
[18]Young L G, McGirr L, Valli V E, et al. Vomitoxin in corn fed to young pigs[J]. J Anim Sci,1983, 57:655-664.
[19]Prelusky D B, Trenholm H L. The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swing[J]. Nat Toxins,1993,1:296-302.
[20]R G Rotter, B K Thompson, H L, Trenholm, et al. A prelimin ary examination of potential inter actions between deoxynivalenol (DON) and other selected Fasariummetabolites in growing pigs[J]. Canadian Journal of Animal Science,1992,72:107-116.
[21]P Pinton, J P Nougayrede, J C del Rio, et al. The food contaminant deoxynivalenol decreases intestinal barrier function and reduces claudin expression[J]. Toxicol. Appl. Pharmaco,237,2009, 41-48.
[22]M Kolf-Clauw, J Castellote, B Joly, et al. Development of a pig jejunal explant culture for studying the gastrointestinal toxicity of the mycotoxin deoxynivalenol. histopathological analysis[J]. Toxicol. In Vitro,2009,23:1580-1584.
[23]Ito E, Okusu M, Terao, et al. Light and scanning electron microscopical observations on gastrointestinal tracts injured by trichothecenes[J],1993,38:11-18.
[24]Sergeev I N, Kravchenko L V, Piliia, et al. The effect of the trichothecene mycotoxin deoxynivalenol (vomitoxin) on calcium homeostasis, vitamin D metabolism and receptors in rats[J]. Vopr Med Khim,1990,36(5):26-31.
[25]W A Awad, J Bohm, E, Razzazi-Fazeli, Effects of feeding deoxynivalenol contaminated wheat on growth performance, organ weights and histological parameters of intestine of broiler chickens[J]. Anim Physiol Anim Nutr,2006,90:32-37.
[26]W A Awad, K Ghareeb, J Bohm, et al. The impact of the fusarium toxin deoxynivalenol (DON) on poultry[J]. Int J Poult Sci,2008,7:827-842.
[27]T Sergent, M Parys, SGarsou, et al. Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations[J]. Toxico Lett, 2006,164:167-176.
[28]李群伟,侯海峰,李亚鲁等.脱氧雪腐镰刀菌烯醇致家兔多脏器损伤的实验观察[J].中国地方病防治杂志,2007,22(1)：19-22.
[29]Hara-Kudo Y, Sugita-KonishiY, Kasuga F, et al. Effects of deoxynivalenol on Salmonella enteritidis infection[J]. Mycotoxins,1996,42:51-56.
[30]Dr. Frank Iverson, Cheryl Armstrong, Eduardo Nera, et al. Chronic Feeding Study of deoxynivalenol in B6C3F1 male and female mice [J]. Teratogenesis, Carcinogenesis, and Mutagenesis.1995,15(6):283-306.
[31]Doll S, Goyarts T, Rothkotter, H J, et al. Effects of deoxynivalenol on immunohistological parameters in pigs [J]. Mycotoxin Research.2006.22(3):178-182.
[32]Tiemann U, Danicke S. In vivo and in vitro effects of the mycotoxins zearalenone and deoxynivalenol on different non-reproductive and reproductive organs in female pigs:A review [J]. Food additives and contaminants,2007,24(3):306-314.
[33]Dumitrescu G, Drinceanu D, Stef L, et al. Alteration on the histological structure of some organs induced by low levels of don mycotoxin in weaned piglets [J]. Archiva Zootechnica,2008,11(2): 12-20.
[34]Tiemann U, Brussow K P, Jonas L, et al. Effectsof diets with cereal grains contaminated by graded levels of two Fusarium toxins on selectedimmunological and histological parameters of spleeningilts[J]. Journal of Animal Science,2006,84:236-245.
[35]L F Kubena, W E Huff, R B Harvey, et al. Influence of Ochratoxin A and Deoxynivalenol on Growing Broiler Chicks[J]. Poult Sci,1988,67 (2):253-260.
[36]Moon YuSeok, Kim HyoungKab, Suh HyunHo, et al. Toxic alterations in chick embryonic liver and spleen by acute exposure to Fusarium-producing mycotoxin deoxynivalenol [J]. Biological & Pharmaceutical Bulletin,2007,30(9):1808-1812.
[37]Yan L Ouyang, Shiguang Li, James J Pestka. Effects of Vomitoxin (Deoxynivalenol) on Transcription Factor NF-κB/Rel Binding Activity in Murine EL-4 Thymoma and Primary CD4+T Cells[J]. Toxicology and Applied Pharmacology,1996,140(2):328-336.
[38]Hui-Ren Zhou, Jack R Harkema, Ding Yan, et al. Amplified proinflammatory cytokine expression and toxicity in mice coexposed to lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) [J]. Journal of Toxicology and Environmental Health, Part A:Current Issues. 1999,57(2):115-136.
[39]Thuvander A, Wilkman C, Gadhasson I. In vitro exposure of human lymphocytes to trichothecenes: individual variation in sensitivity and effects of combined exposure on lymphocyte function[J]. Food Chem Toxicol,1999,37(6):639-648.
[40]T Malovrh, B Jakovac-Strajn. Feed contaminated with toxins alter lymphocyte proliferation and apoptosis in primiparous sows during the perinatal period[J]. Food and Chemical Toxicology, 2010,48(10):2907-2912.
[41]Sun XM, Zhang XH, Wang HY, et al. Effects of sterigmatocystin, deoxynivalenol and aflatoxin G1 on apoptosis of human peripheral blood lymphocytes in vitro [J]. Biomed Environ Sci,2002, 15(2):145-152.
[42]李月红,张祥宏,王俊灵,等.脱氧雪腐镰刀菌烯醇对小鼠胸腺细胞凋亡和增殖的影响[J].中国病理生理杂志.2002,18(7)：778-781.
[43]Zahidul Islam, James J Pestka. Role of IL-1(3 in Endotoxin Potentiation of Deoxynivalenol-Induced Corticosterone Response and Leukocyte Apoptosis in Mice [J]. Toxicological Sciences, 2003,74:93-102.
[44]Pestka J J, Yan D, King L E. Flow cytom etric analysis of the effects of in vitro exposure to vomitoxin (deoxynivalenol) on apoptosis in murine T, B and IgA+ cells [J]. Food Chem Toxicol, 1994,32:1125-1136.
[45]Zhou H R, Islam Z, Pestka J J. Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol[J]. Toxicol Sci,2005,87(1):113-122.
[46]J J Pestka. Deoxynivalenol-induced IgA production and IgA nephropathy-aberrant mucosal immune response with systemic repercussions. Toxicol Lett,2003,140:287-295.
[47]T Goyarts, S Danicke, U Tiemann, et al. Effect of the Fusarium toxin deoxynivalenol (DON) on IgA, IgM and IgG concentrations and proliferation of porcine blood lymphocytes[J]. Toxicol, In Vitro,2006,20:858-867.
[48]Tanja Goyarts, Nicola Grove, Sven Danicke. Effects of the deoxynivalenol from naturally contaminated wheat given subchronically or as one single dose on the protein synthesis of peripheral blood lymphocytes and plasma proteins in the pig[J]. Food and Chemical Toxicology, 2006,44(12):1953-1965.
[49]Sandra W M van Kol, Peter J M Hendriksen, Henk van Loveren, et al. deoxynivalenol on gene expression in the murine thymus [J]. Toxicology and Applied Pharmacology,2011,250(3):299- 311.
[50]Kei-ichi Sugiyama, Masashi Muroi, Ken-ichi Tanamoto, et al. Deoxynivalenol and nivalenol inhibit lipopolysaccharide-induced nitric oxide production by mouse macrophage cells[J]. Toxicology Letters.2010,192(2):150-154.
[51]Yann J Wache, Laila Hbabi-Haddioui, Laurence Guzylack-Piriou, et al. The mycotoxin Deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages[J]. Toxicology,2009,262(3):239-244.
[52]C Banotai, D M Greene-McDowelle, J I Azcona-Olivera, et al. Effects of intermittent vomitoxin exposure on body weight, immunoglobulin levels and haematuria in the B6C3F1 mouse[J]. Food and Chemical Toxicology.1999,37(4):343-350.
[53]J I Azcona-Olivera, Y-L Ouyang, R L Warner, et al. Effects of vomitoxin (Deoxynivalenol) and cycloheximide on IL-2,4,5 and 6 secretion and mRNA levels in murine CD4+cells [J]. Food and Chemical Toxicology.1995,33(6):433-441.
[54]Hui-Ren Zhou, Ding Yan, James J Pestka. Differential Cytokine mRNA Expression in Mice after Oral Exposure to the Trichothecene Vomitoxin (Deoxynivalenol):Dose Response and Time Course[J]. Toxicology and Applied Pharmacology,1997,144(2):294-305.
[55]H R Zhou, D Yan, J J Pestka. Induction of cytokine gene expression in mice after repeated and subchronic oral exposure to vomitoxin (deoxynivalenol):differential toxin-induced hyporesponsiveness and recovery[J]. Toxicol Appl Pharmacol,1998,151:347-358.
[56]Yoshiko Sugita-Konishi. Deoxynivalenol and cycloheximide on IL-2,4,5 and 6 secretion and mRNA levels in murine CD4+ cells [J]. Food and Chemical Toxicology,1995,33(6):433-441.
[57]Z Islam, J S Gray, J J Pestka,. p38 mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes[J]. Toxicol Appl Pharmacol,2005,213:235-244.
[58]Meky F A, Haridie, L J, Evans, S W, et al. Deoxynivalenol-induced immunomodulation of human lymphocyte proliferation and cytokine production. Food and Chemical Toxicology,2001,39:827-836.
[59]Hymery N, Sibiril Y, Parent-Massin D. In vitro effects of trichothecenes on human dendritic cells. Toxicology in Vitro,2006,20(6):899-909.
[60]C J Amuzie, J R Harkema, J J Pestka. Tissue distribution and proinflammatory cytokine induction by the trichothecene deoxynivalenol in the mouse:comparison of nasal vs. oral exposure[J]. Toxicology,2008,248:39-44.
[61]C J Amuzie, J Shinozuka, J J Pestka. Induction of suppressors of cytokine signaling by the trichothecene deoxynivalenol in the mouse[J]. Toxicol Sci,2009,111:277-287.
[62]L C Borish, J W Steinke. Cytokines and chemokines[J]. Allergy Clin Immunol,2003,111:460-475.
[63]R W Johnson. Immune and endocrine regulation of food intake in sick animals[J]. Domest Anim Endocrinol,1998,15:309-319.
[64]Susanne Doll, Jan A Schrickx, Sven Danicke. Deoxynivalenol-induced cytotoxicity, cytokines and related genes in unstimulated or lipopolysaccharide stimulated primary porcine macrophages[J]. Toxicology Letters,2009,184(2):97-106.
[65]Kinser S, Jia Q S, Li M X, et al. Gene expression profiling in spleens of deoxynivalenol-exposed mice:immediate early genes as primary targets [J]. Journal of Toxicology and Environmental Health, Part A.2004,67(18):1423-1441.
[66]James J Pestka, Chidozie J Amuzie. Tissue distribution and proinflammatory cytokine gene expression following acute oral exposure todeoxynivalenol:Comparison of weanling and adult mice[J]. Food and Chemical Toxicology,2008,468(8):2826-2831.
[67]Philippe P, Francesc A, Erwan B, et al. Ingestion of deoxynivalenol(DON) contaminated feed alters the pig vaccinal immune responses [J]. Toxicology Letters,2008,177:215-222.
[68]Jacqueline Van De Walle, Beatrice Romier, Yvan Larondelle, et al. Influence of deoxynivalenol on NF-κB activation and IL-8 secretion in human intestinal Caco-2 cells[J]. Toxicology Letters, 2008,177(3):205-214.
[69]D Parent-Massin. Haematotoxicity of trichothecenes[J]. Toxicology Letters,2004,153(1):75-81.
[70]Yann J Wache, Laila Hbabi-Haddioui, Laurence Guzylack-Piriou, et al. The mycotoxin Deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages[J]. Toxicology,2009,262(3):239-244.
[71]Stefania M, Rosario R, Gluseppe B, et al. Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in J774A.1 murine macrophages[J]. Toxicology Letters,2009,189:21-26.
[72]Maika Konigs, Marlies Lenczyk, Gerald Schwerdt, et al. Cytotoxicity, metabolism and cellular uptake of the mycotoxin deoxynivalenol in human proximal tubule cells and lung fibroblasts in primary culture[J]. Toxicology,2007,240(1):48-59.
[73]Lean Mc. The phytotoxicity of Fusarium metabolites:an update since 1989[J]. Mycopathologia, 1996,133:163-179.
[74]David L Bunner, Elena R Morris. Alteration of multiple cell membrane functions in L-6 myoblasts by T-2 toxin:An important mechanism of action[J]. Toxicology and Applied Pharmacology,1988,92(1):113-121.
[75]Chang II-Moo, Mar Woong-Chon. Effect of T-2 toxin on lipid peroxidation in rats:Elevation of conjugated diene formation[J]. Toxicology Letters.1988,40(3):275-280.
[76]S K Suneja, D S Wagle, G C Ram. Effect of oral administration of T-2 toxin on glutathione shuttle enzymes, microsomal reductases and lipid peroxidation in rat liver [J]. Toxicon,1989, 27(9):995-1001.
[77]J H Kouadio, T A Mobio, I Baudrimont, et al. Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin Bl in human intestinal cell line Caco-2[]J. Toxicology,2005,213:56-65.
[78]Xiaoou Zhang, Liping Jiang, Chengyan Geng, et al. The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells[J]. Toxicon,2009,54(4):513-518.
[79]Diana Dinu, Gabriela Oana Bodea, Corina Diana Ceapa, et al. Adapted response of the antioxidant defense system to oxidative stress induced by deoxynivalenol in Hek-293 cells[J]. Toxicon,2011, 57(7):1023-1032.
[80]J M Mates. Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology[J]. Toxicology,2000,153:83-104.
[81]曹峻岭,熊咏民,张矢远,等.真菌毒素DON.T-2和NIV对培养软骨细胞作用的实验研究[J].中国地方病防治杂志,1995,10(2)：69-71.
[82]王会艳,孙旭明,张祥宏,等.脱氧雪腐镰刀菌烯醇、黄曲霉毒素G对体外培养人外周血淋巴细胞凋亡影响的研究[J].卫生研究,1999,28(2)：102-104.
[83]李斌,郭红卫.AFB1和DON对大鼠原代肝细胞DNA损伤的研究[J].中国公共卫生,2001,17(12)：1115-1116.
[84]S Knasmuller, N Bresgen, F Kassie, et al. Genotoxic effects of three Fusarium mycotoxins, fumonisin B1, moniliformin and vomitoxin in bacteria and in primary cultures of rat hepatocytes[J]. Mutat Res,1997,391:39-48.
[85]C C Hsia, J L Wu, X Q Lu, et al. Natural occurrence and clastogenic effects of nivalenol, deoxynivalenol,3-acetyl-deoxynivalenol,15-acetyldeoxynivalenol, and zearalenone in corn from a high-risk area of esophageal cancer[J]. Cancer Detect Prev,1988,13:79-86.
[86]D H Li, Y Sun, X Y Luo, et al. Genotoxicity of deoxynivalenol on CHL cells[J]. Chin J Food Hyg, 1992,4:40-43.
[87]T Frankic, T Pajk, V Rezaret al. The role of dietary nucleotides in reduction of DNA damage induced by T-2 toxin and deoxynivalenol in chicken leukocytes[J]. Food Chem Toxicol,2006,44, 1838-1844.
[88]S Bony, M Carcelen, L Olivier, et al. Genotoxicity assessment of deoxynivalenol in the Caco-2 cell line model using the comet assay[J]. Toxicol Lett,2006,166:67-76.
[89]林林,孙树秋.脱氧雪腐镰刀菌烯醇致Vero细胞核基因组DNA损伤与修复的彗星实验观察[J].中国地方病防治杂志.2004,19(3)：139-141.
[90]Hauptman K, Tichy F, Knotek Z, et al. Clincial diagnostics of hepatopathies in small mammals: Evaluation of importance of individual methods[J]. Acta Veterinaria,2001,70:297-311.
[91]Yang G, Jarvis B B, Chung Y, et al. Apoptosis induction by the satratoxins and other trichothecene mycotoxins:Relationship to ERK, p38 MAPK and SAPK/JNK Activation [J]. Toxicol Appl Pharmacol,2000,164(2):149-160.
[92]Zhou H R, Lau A S, Pestka J J. Role of Double-Stranded RNA-Activated Protein Kinase R (PKR) in Deoxynivalenol-Induced Ribotoxic Stress Response[J]. Toxicol Sci,2003,74(2):335-344.
[93]Zhou H R, Jia Q, Pestka J J. Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase Hck[J]. Toxicol Sci,2005,85(2):916-926.
[94]Zhou H R, Islam Z, Pestka J J. Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol[J]. Toxicol Sci,2005,87(1):113-122.
[95]Fatma Bensassi, Cindy Gallerne, Ossama Sharaf E1 Dein, et al. Involvement of mitochondria mediated apoptosis in deoxynivalenol cytotoxicity[J]. Food and Chemical Toxicology,2012, 50(5):1680-1689.
[96]Pestka J, Zhou H R. Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants [J]. Toxicol Sci,2006,92(2):445-455.
[97]Fatma Bensassi, Emna El Golli-Bennour, Salwa Abid-Essefi, et al. Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells[[J]. Toxicology,2009,264(1-2):104-109.
[98]O Mikami, S Yamamoto, N Yamanaka, et al. Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol[J]. Toxicology,2004,204:241-249.
[99]Stefania Marzocco, Rosario Russo, Giuseppe Bianco, et al. Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in J774A.1 murine macrophages. Toxicology Letters.2009,189(1): 21-26.
[100]Anton A Tonshina, Vera V Teplovab, Maria A Andersson, et al. The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation, oxidative phosphorylation and ion homeostasis. [J]. Toxicology,2010,276(1):49-57.
[101]彭双清,杨进生.镰刀菌毒素脱氧雪腐镰刀菌烯醇对心肌细胞Ca通道的阻滞作用[J].中国预防医学杂志.2004,5(4)：241-243.
[102]Shiguang Li, Yan L Ouyang, Wumin Dong, et al. Superinduction of IL-2 Gene Expression by Vomitoxin (Deoxynivalenol) Involves Increased mRNA Stability[J]. Toxicology and Applied Pharmacology,1997,147(2):331-342.
[103]Shu-shyan Wong, Richard C Schwartz, James J Pestka. Superinduction of TNF-a and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization [J]. Toxicology. 2001,161(1-2):139-149.
[104]Shiguang Li, Yanli Ouyanga, Gi-Hyeok Yang, et al. Modulation of Transcription Factor AP-1 Activity in Murine EL-4 Thymoma Cells by Vomitoxin (Deoxynivalenol)[J]. Toxicology and Applied Pharmacology,2000,163(1):17-25.
[105]Shu-Shyan Wong, Hui-Ren Zhou, James J Pestka. Effects Of Vomitoxin (Deoxynivalenol) On The Binding Of Transcription Factors Ap-1, Nf-Kb, And Nf-116 In Raw 264.7 Macrophage Cells[J]. Journal of Toxicology and Environmental Health, Part A:Current Issues, 2002,65(16):1161-1180.
[106]Yuseok Moon, James J Pestka. Deoxynivalenol-induced mitogen-activated protein kinase phosphorylation and IL-6 expression in mice suppressed by fish oil[J]. The Journal of Nutritional Biochemistry,2003,14(12):717-726.
[107]莫国艳,黄仁彬,林军,等.六月青萃取物对免疫抑制小鼠的影响[J]. Herald of Medicine, 2007,26(11):1264-1265.
[108]赵虎,杨在宾,杨维仁,等.日粮中添加玉米赤霉烯酮对仔猪生产性能和免疫功能影响的研究[J].山东农业大学学报(自然科学版),2009,40(4)：489-494.
[109]Jillian Calemine, Julie Zalenka, Ebru Karpuzoglu-Sahin, et al. The immune system of geriatric mice is modulated by estrogenic endocrine disruptors (diethylstilbestrol, a-zearalanol, and genistein):Effects on interferon-γ[J]. Toxicology,2003,194, (1-2):115-128
[110]Danicke S.1;Ueberschar K.-H.2;Valenta H., et al. Effects of graded levels of Fusarium-toxin-contaminated wheat in Pekin duck diets on performance, health and metabolism of deoxynivalenol and zearalenone[J]. British Poultry Science,2004,45(2):264-272.
[111]Samir Abbes, Jalila Ben Salah-Abbes, Zouhour Ouanes, et al. Preventive role of phyllosilicate clay on the Immunological and Biochemical toxicity of zearalenone in Balb/c mice [J]. International Immunopharmacology,2006,6:1251-1258.
[112]Collins T F, Sprando R L, Black T N, et al. Effects of zearalenone on in utero development in rats[J]. Food Chem Toxicol.2006,44(9):1455-1465.
[113]M. Abdelhamid, I. P. Kelad, M. M. Ali, S. A. El-Ayouty. Influence of Zearalenone on Some Metabolic, Physiological and Pathological Aspects of Female Rabbits at Two Different Ages[J]. Archiv fur Tieremaehrung,1992,42(1):63-70.
[114]Abdelhamid A M, Kelada I P., Ali M M, et al. Influence of zearalenone on some metabolic, physiological and pathological aspects of female rabbits at two different ages[J]. Archives of Animal Nutrition,1993,42(1):63-70.
[115]Obremski K, Gajecki M, Otrocka-Domagaa I, et al. Clinical case of rabbit zearalenone mycotoxicosis[J]. Medycyna Weterynaryjna,2005,61(4):458-461.
[116]Popova-Ralcheva S, Gudev D, Yanchev I, et al. Effect of the mycotoxins zearalenone and aflatoxin B1 on some biochemical indices, internal organs and glands in chicks. II. Possibilities to antagonize their effect by Cleanotox. [J]. Zhivotnov'dni Nauki,2003,40(3-4):100-104.
[117]Andretta, I., Lovatto, P. A., Hauschild, L, et al. Feeding of pre-pubertal gilts with diets containing zearalenone[J]. Arquivo Brasileiro de Medicina Veterinaria e Zootecnia,2008,60(5): 1227-1233.
[118]M. L. Biehl, D. B. Prelusky, G. D. Koritz, K. E. Hartin, W. B. Buck, H. L. Trenholm. Biliary Excretion and Enterohepatic Cycling of Zearalenone in Immature Pigs[J]. Toxicology and Applied Pharmacology,1993,121(1):152-159.
[119]赵虎,杨在宾,杨维仁,等.玉米赤霉烯酮对仔猪生产性能和内脏器官发育影响的研究[J].粮食与饲料工业.2008,10：37-38
[120]M. Dong, X. J. He, P. Tulayakul, et al. The toxic effects and fate of intravenously administered zearalenone in goats [J]. Toxicon,2010,55(2-3):523-530.
[121]钱利纯,罗兆正.ZEA对畜禽的毒害作用研究进展[J].黑龙江畜牧兽医,2005,9：78-80.
[122]Pestka J J, Tai J H, Witt M F, et al. Suppression of immune response in the B6C3F1 mouse after dietary exposure to the fusarium mycotoxins deoxynivalenol(vomitoxin) and zearalenone[J]. Food Chem Toxic,1987,25;297-304
[123]Vlata Z, Porichis F, Tzanakakis G, et al. A study of zearalenone cytotoxicity on human peripheral blood mononu clear cells[J]. Toxicol Lett,2006,165(3):274-281.
[124]梁梓森,许利娜,马勇江等.玉米赤霉烯酮对小鼠胞腺细胞凋亡的影响[J].中国兽医杂志.2009,45(7)；88-90
[125]Lioi MB, Santoro A, Barbieri R, et al. Ochratoxin and zearalenone;a comparative study on genotoxic effects and cell death induced in bovine lymphocytes [J]. Mutation Research.2004. 557;19-24.
[126]Berek L, Petri I B, Mesterhazy A, et al. Effects of mycotoxins on human immune functionsin vitroolToxicologyin Vitro,2001,15:25-30
[127]Speranda Marcela, Liker B, Sperand T, et al. Haematological and biochemical parameters of weaned piglets fed on fodder mixture contaminated by zearalenone with addition of clinoptilolite [J]. Acta Veterinaria (Beograd),2006,56(2-3):121-136.
[128]马勇江,许利娜,李玉谷,等.玉米赤霉烯酮对小鼠脾淋巴细胞凋亡的影响[J].家畜生态学报.2009,30(1)；52-56.
[129]Forsell, Pestka. Relation of 8-ketotrichothecene and zearalenone analog structure to inhibition of mitogen-induced human lymphocyte blastogenesis [J]. Appl. Environ. Microbiol, 1985,50:1304-1307
[130]Marin M L, Murtha J, Dong W, et al. Effects of mycotoxins on cytokine production and proliferation in EL-4 thymoma cells[J]. Journal of Toxicol Environ Health,1996,48:379-396.
[131]Eriksen G S, Alexander J. Fusatium toxins in cereals-a risk assessment [A]. Nordic Council of Ministers[C]. Tema Nord Copenhagen,1998.502;7-58
[132]Murata H, Sultana P, Shimada N, et al. Structure activity relationships among zearalenone and its derivatives based on bovine neutrophil chemiluminescence. Vet Hum Toxicol,2003,45,18-20.
[133]Daniela E. Marin, Ionelia Taranu, Radu Burlacu, et al. Effects of zearalenone and its derivatives on the innate immune response of swine[J]. Toxicon,2010,56(6):956-963.
[134]范小龙,刘长永,剡海阔,等.玉米赤霉烯酮对小鼠脾淋巴细胞增殖及分泌细胞因子的 影响.中国畜牧兽医,2011,38(5)：48-54.
[135]Pestka J, Zhou H R. Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants [J]. Toxicol Sci,2006,92(2):445-455.
[136]Conkova E, Laciakova A, Pastorova B, et al. The effect of zearalenone on some enzymatic parameters in rabbits [J]. Toxicol Lett,2001,121;145-149.
[137]Maaroufi K, Chekir L, Creppy E E, et al. Zearalenone induces modifications of haematological and biochemical parameters in rats[J]. Toxicon,1996,34;535-540.
[138]Minervini F, Dell' Aquila M. E., Maritato F, et al., Toxic effects of the mycotoxin zearalenone and its derivatives on in vitro maturation of bovine oocytes and 17β-estradiol levels in mural granulosa cell cultures[J]. Toxicology in Vitro,2001,15:489-495.
[139]Trevor K., Diaz S. G., and Swamy H. V. L. N. Current concepts in mycotoxicoses in swing. In:Duarte Diaz, (Eds), The mycotoxin blue book. Nottingham University Press,2004:239-240.
[140]Aim H, Greising T, Brussow K. P., et al. The influence of the mycotoxins deoxynivalenol and zearalenol on in vitro maturation of pig oocytes and in vitro culture of pig zygotes[J]. Toxicology in Vitro,2002,16:43-48.
[141]Aim H., Brussowa K. P., Tomer H., et al. Influence of Fusarium-toxin contaminated feed on initial qulity and meiotic competence of gilt oocytes[J]. Reproductive Toxicology,2006,22:44-50.
[142]I. A. Tsakmakidis, A. G. Lymberopoulos, C. Alexopoulos, et al. In vitro effect of zearalenone and α-zearalenol in boar sperm characteristics and acrosome reaction[J]. Reprod. Domest. Anim.,2006,41:394-401.
[143]Kuiper G G J M, Lemmen J G, Carlsson B. Interaction of estrogenic chemical and phytostrogens with estrogen receptor [J]. Endocrinolgy,1998,139:4252-4263.
[144]Dees C, Foster J S, Ahamed S. Dietary estrogens stimulate human breast cells to enter the cell cycle [J]. Environ Health Perspect,1997,105(suppl 3):633-636;
[145]Sheehan D M, Branham W S, Medlock KL. Estrogenic activity of zearalenone and zearalanol in the neonatal rat uterus [J]. Teratology,1984,29:383-392
[146]Olsen M, Petterson H, Kiessling KH. Reduction of zearalenone to zearalenol in female rat liver by 3-hydroxysteroid dehydrogenase[J]. Acta Pharmacol Et Toxicol,1986(48):157-161.
[147]James H K, Theophile A M, Isabelle B, et al. Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2 [J]. Toxicology,2005,213:56-65.
[148]E. Ferrer, A. Juan-Garcia, G Font, et al. Reactive oxygen species induced by beauvericin, patulin and zearalenone in CHO-K1 cells. [J]. Toxicology in Vitro,2009,23(8):1504-1509.
[149]Quane Z, Abid S, Ayed I, et al. Induction of micronulei by zearalenone in vero monkey kidney cells and in bone marrow cells of mice;protective effect of vitamin E [J]. Mutat Res,2003, 538:63-70.
[150]Abid-Essefi S, Ouanes Z, Hassen W, et al. Cytotoxicity, inhibition of DNA and protein syntheses and oxidative damage in cultured cells exposed to zearalenone[J]. Toxicology in Vitro, 2004.18:467-474.
[151]J Y Yang, G X Wang, J. L. Liu, et al. Toxic effects of zearalenone and its derivatives a zearalenol on male reproductive system in mice[J]. Reprod Toxicol,2007,24:381-387.
[152]I Ayed-Boussema, Z Ouanes, H Bacha, et al. Toxicities induced in cultured cells exposed to zearalenone:apoptosis or mutagenesis?[J]. Biochem Mol Toxicol,2007,21:136-144.
[153]E El-Golli, W Hassen, A Bouslimi, et al. Induction of Hsp70 in Vero cells in response to mycotoxins cytoprotection by sub-lethal heat shock and by vitamin E[J]. Toxicol Lett,2006,16: 122-130.
[154]B E El-Golli, C. Bouaziz, M. Ladjimi, et al. Comparative mechanisms of zearalenone and ochratoxin A toxicities on cultured HepG2 cells:in oxidative stress a common process[J]. Environ Toxicol,2009,24:538-548.
[155]E Benzoni, F Minervini, A. Giannoccaro, et al. Influence of in vitro exposure to mycotoxin zearalenone and its derivatives on swine sperm quality[J]. Reprod Toxicol,2008,25:461-467.
[156]I A Tsakmakidis, A G Lymberopoulos, T. A. A. Khalifa, et al. Evaluation of zearalenone and a-zearalenol toxicity on boar sperm DNA integrity[J]. Appl. Toxicol,2008,28,681-688.
[157]Wafa Hassen, Imen Ayed-Boussema, Amaia Azqueta Oscoz, et al. The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells:Oxidative DNA damage, gluthatione depletion and stress proteins induction[J]. Toxicology,2007,232(3):294-302
[158]Zouhour Ouanes-Ben Othmen, Emna El Golli, Salwa Abid-Essefi, et al. Cytotoxicity effects induced by Zearalenone metabolites, a Zearalenol and β Zearalenol, on cultured Vero cells [J]. Toxicology,2008,252(1-3):72-77
[159]郭炳虹,张佳颖.F-2毒素致DNA损伤研究[J].黑龙江医学,2004,28(3)：193-194.
[160]Quanes Z, Aved-Boussema, Baati T, et al. Zearalenone induces chromosome aberrations in mouse bone marrow:preventive effect of 17beta-estradiol, progesterone and vitamin E[J]. Mutat Res,2005,565 (2):139-149.
[161]孙美乐,王博文.玉米赤霉烯酮对体外培养大鼠肝细胞的影响[J]中国地方病防治杂志,1997,2：69-70.
[162]严继承,郑一凡,曾群力,等.玉米赤霉烯酮对细胞间隙连接通讯的影响[J].卫生毒理学杂志,2004,18(3)：160-162.
[163]邓友田,袁慧.玉米赤霉烯酮毒性机理研究进展[J].动物医学进展,2007,28(2)：89-92.
[164]Yosra Ayed, Imen Ayed-Boussema, Zouhour Ouanes, et al. In vitro and in vivo induction of chromosome aberrations by alpha-and beta-zearalenols:Comparison with zearalenone[J]. Mutation Research/Genetic Toxicology and Environmental Mutagenesis,2011,726(1):42-46.
[165]F Minervini, G M Lacalandra, A Filannino, et al. Effects of in vitro exposure to natural levels of zearalenone and its derivatives on chromatin structure stability in equine spermatozoa[J]. Theriogenology,2010,73:392-403.
[166]Abid-Essefi S, Baudrimont I, Hassen W, et al. DNA fragmentation, apoptosis and cell cycle arrest induced by zearalenone in cultured DOK, Vero and Caco-2 cells;prevention by Vitamin E[J]. Toxicology,2003,192;237-248.
[167]S Abid-Essefi, C Bouaziz, E E Golli-Bennour, et al. Comparative study of toxic effects of zearalenone, and its two major metabolites alpha-zearalenol and beta-zearalenol on cultured human Caco-2 cells[J]. Biochem. Mol. Toxicol.,2009,23,233-243.
[168]Kim I H, Son H Y, Cho S W, et al. Zearalenone induces male germ cell apoptosis in rats[J]. Toxicol Lett.2003,138(3):185-192.
[169]余增丽,张立实,吴德生.玉米赤霉烯酮对乳腺癌细胞MCF-7增殖和凋亡的影响[J].中国预防医学杂志,2005,39(5)：328-331.
[170]U Tiemann, T Viergutza, L Jonasb, et al. Influence of the mycotoxins α-and β-zearalenol and deoxynivalenol on the cell cycle of cultured porcine endometrial cells[J]. Reproductive Toxicology,2003,17(2):209-218.
[171]符达.玉米赤霉烯酮对SD大鼠卵巢p53第八外显子突变的研究[D].湖南农业大学硕士论文2005.
[172]曹林枝.p53基因及其分子生物学作用[J].中国临床医药,2003,5(1)；77-80.
[173]Ji-Yeon Yu, Zhong-Hua Zhenga, Young-Ok Son, et al. Mycotoxin zearalenone induces AIF-and ROS-mediated cell death through p53-and MAPK-dependent signaling pathways in RAW264.7 macrophages [J]. Toxicology in Vitro,2011,25(8):1654-1663
[174]H L Trenholm, B K Thompson, B C Foster, et al. Effects of feeding diets containing Fusarium (naturally) contaminated wheat or pure deoxynivalenol (DON) in growing pigs[J]. Canadian Journal of Animal Science,1994,74(2):361-369.
[175]G J A Speijers, M H M Speijers. Combined toxic effects of mycotoxins[J]. Toxicology Letters,2004,153:91-98.
[176]K C Williams, B J Blaney, R T Peters. Pigs fed Fusarium-infected maize containing zearalenone and nivalenol with sweeteners and bentonite[J]. Livestock Production Science,1994, 39(3):275-281.
[177]Trenholm H L, Friend D W, Thompson, et al. Effects of zearalenone and deoxynivalenol combinations fed to pigs[J]. Pro Jpn Assoc Mycotox,1988, Suppll:101-102.
[178]H V L N Swamy, T K Smith, E J MacDonald. Effects of feeding blends of grains naturally contaminated with mycotoxins Fusarium on brain regional neurochemistry of starter pigs and broiler chickens[J]. Journal Of Animal Science,2004,82:2131-2139.
[179]Danicke S, Brussow K P, Goyarts T, et al. On the transfer of the Fusarium toxins deoxynivalenol(DON) and zearalenone (ZEA) from the sow to the full-term piglet during the last third of gestation [J]. Food & Chemical Toxicology,2007,45(9):1565-1574.
[180]Tiemann U, BrussowK P, Kuchenmeister U, et al. Changes in the spleen and liver of pregnant sows and full-term piglets after feeding diets naturally contaminated with deoxynivalenol and zearalenone [J]. Veterinary Journal,2008,176:188-196.
[181]Tiemann U, Brussow K P, Dannenberger D, et al. The effect of feeding a diet naturally contaminated with deoxynivalenol (DON) and zearalenone (ZON) on the spleen and liver of sow fetus from day 35 to 70 of gestation [J]. Toxicology letters,2008,179(3):113-117.
[182]Chen Feng, Ma YuLin, Xue ChunYi, et al. The combination of deoxynivalenol and zearalenone at permitted feed concentrations causes serious physiological effects in young pigs[J]. Journal of Veterinary Science,2008,9(1):39-44.
[183]苏军.镰刀菌毒素对猪的抗营养效应及其机制研究.[硕士学位论文].雅安：四川农业大学,2008.
[184]Yegani M, Smith T K, Leeson S, et al. Effects of Feeding Grains Naturally Contaminated with Fusarium Mycotoxins on Performance and Metabolism of Broiler Breeders[J]. Poultry science,2006,85(9):1541-1549.
[185]T K Smith. Contemporary concepts in the aetiology and prevention of mycotoxicoses in livestock and poultry[J]. The mycotoxins factbook:Food and Feed topics,2006:313-326.
[186]Danicke S, Ueberschar K-H, Halle I, et al. Effect of addition of a detoxifying agent to laying hen diets containing uncontaminated or Fusarium toxin-contaminated maize on performance of hens and on carryover of zearalenone[J]. Poul Sci,2002,81:1671-1680.
[187]M Levkut, V Revajova, Z Slaminkova, et, al. Lymphocyte subpopulations in blood and duodenal epithelium of broilers fed diets contaminated with deoxynivalenol and zearalenonefj]. Animal Feed Science and Technology,2011,165(3-4):210-217.
[188]Boeira L S, Bryce J H, Stewart G G, et, al. The effect of combination of Fusarium mycotoxins (deoxynivalenol, zearalenone and fumonisin B1)on growth of brewing yeasts[J]. J Appl Microbiol, 2000,88:388-403.
[189]Coppock R W, Mostrom M S, Sparling C G, et, al. Apparent zearalenone intoxication in a dairy herd from feeding spoiled acid-treated corn[J]. Veterinary and Human Toxicology,1990, 32(3):246-248.
[190]James H Kouadioa, Se'bastien D Danob, Serge Moukhac, et al. Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells[J]. Toxicon,2007,49: 306-317.
[191]Abdelhamid A M. Effect of feeding rabbits on naturally moulded and mycotoxin contaminated diet[J]. Archives of Animal Nutrition,1990,40(1-2):55-63.
[192]H A C Atkinson, K Miller. Inhibitory effect of deoxynivalenol,3-acetyldeoxynivalenol and zearalenone on induction of rat and human lymphocyte proliferation[J]. Toxicology Letters,1984, 23(2):215-221.
[193]Shinya Nagafuji, Hikaru Okabe, Hiroshige Akahane, et, al. Trypanocidal constituents in plants 4. withanolides from the aerial parts of physalis angulata[J]. Biological and Pharmaceutical Bulletin,2004,27(2):193-197.
[194]张诚,陈幸华,张曦等.WST-8检测培养小鼠脾NK细胞增殖及杀伤活性的研究.西南国防医药,2008,18(3)：313-315.
[195]Okamura M, Lillehoj H S, Raybourne R B, et, al. Cell-mediated immune responses to a killed Salmonella enteritidis vaccine:lymphocyte proliferation, T-cell changes and interleukin-6(IL-6), IL-1, IL-2, and IFN-γ production[J]. Comp Immun Microbiol Infect Dis,2004,27: 255-272.
[196]K Miller, H A C Atkinson. The In vitro effects of trichothecenes on the immune system[J]. Food and Chemical Toxicology,1986,24(6-7):545-549.
[197]Vermes I, Haanen C, Steffens-Nakken H, et, al. A novel assay for apoptosis, flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein-labeled[J]. Annexin V J Immunol Meth,1995,184:39-51.
[198]Gunnar Sundst(?)l Eriksen, Hans Pettersson. Toxicological evaluation of trichothecenes in animal feed[J] Animal Feed Science and Technology,2004,114(1-4):205-239.
[199]Y Cetin, L B Bullerman. Cytotoxicity of Fusarium mycotoxins to mammalian cell cultures as determined by the MTT bioassay[J]. Food and Chemical Toxicology,2005,43(5):755-764.
[200]韩贻仁.分子细胞生物学[M].北京：科学出版社,2003：648-661.
[201]Shabani A, Rabbani A. Lead nitrate induced apoptosis in alveolar macrophages from rat lung[J]. Toxicology,2000,149:109-114.
[202]H De La Fuente, D Portales-Perez, L Baranda, et al. Effect of arsenic, cadmium and lead on the induction of apoptosis of normal human mononuclear cells[J] Clinical & Experimental Immunology,2002,129(1):69-77.
[203]夏世钧,吴中亮.分子毒理学基础[M].武汉：湖北科学技术出版社,2001：87-90.
[204]Trevor F Slater. Free-radical mechanisms in tissue injury[J]. Biochem,1984,222:1-15.
[205]Tanusree Sen, Nikantha Sen, Gayatri Tripathi, Chatterjee Uttara, Sasanka Chakrabarti. Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria[J]. Neurochem Int,2006,49:20-27.
[206]Etsuo Niki, Yasukazu Yoshida, Yoshiro Saito, Noriko Noguchi. Lipid peroxidation: mechanism, inhibition, and biological effects[J]. Biochemical and Biophysical Resarch Communications,2005,338:668-676.
[207]Koji Uchida.4-Hydroxy-2-nonenal:a product and mediator of oxidative stress. Progress in Lipid Research,2003,42(4):318-343.
[208]Jian Luo, Riyi Shi. Acroline induced oxidative stress in brain mitochondria[J]. Neurochemistry Interational,2005,46:243-252.
[209]I Ayed-Boussema, C Bouaziz, K Rjiba, et al. The mycotoxin zearalenone induces apoptosis in human hepatocytes (HepG2) via p53-dependent mitochondrial signalling pathway[J]. Toxicology In Vitro,2008,22:1671-1680.
[210]C Bouaziz, O Sharafeldein, E El Golli, et al. Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells[J]. Toxicology,2008,254: 19-28.
[211]Pathak N, Khandelwal S. Influence of cadmium on murine thymocytes:potentiation of apoptosis and oxidative stress[J]. Toxicol Lett,2006,165:121-132.
[212]Scaduto R C, Grotyohann L W. Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J,1999,76:469-477.
[213]Dimri U, Ranjan R, Kumar N, et al. Changes in oxidative stress indices, zinc and copper concentrations in blood in canine demodicosis[J]. Vet Parasitol,2008,154:98-102.
[214]Huxtable R J. Physiological action of taurine[J]. Physiol Revi,1992,72:101-142.
[215]Kelly S A, Havrilla C M, Brady T C, et al. Oxidative stress in toxicology:established mammalian and emerging piscine model systems[J]. Environ Health Perspect,1998,106:375-384.
[216]Findel T, Holbrook N J. Oxidants, oxidative stress and the bilolgy of aging[J]. Nature,2000, 408:239-247.
[217]Bird R P, Draper H H, Effect of malondialdehyde acetaldehyde on cultured mammalian cells: growth, morphology and synthesis of macromolecules[J]. Journal of Toxicology and Environmental Health.1980,6:811-823.
[218]Tomita M, Okuyama T. Determination of malondialdehyde in oxidized biological materials by high-performance liquid chromatography[J].1990,515:391-397.
[219]Pexter D T, Sian J, Rose S, et al. Indices of oxidative stress and mito-chondrial function in individiulas with incidental lewy body disease[J]. Ann Neurol,1994,35:38-44.
[220]Kehrer J P, Mossman B T, Sevanian A, et al. Free radical mechanisms in chemical pathogenesis[J]. Toxicol and Applied Phanrmacol,1998,95:349-356.
[221]Larsen M, Webb G, Kennington S, et al. Mannitol in cardioplegia as an oxygen free radical scavenger measyred by malondialdehyde[J]. Perfusion,2002,17(1):51-55.
[222]Sies H, Akerboom T P. Glutathione disulfide(GSSG)efflux from cells and tissues[J]. Method Enzymol,1984,105:445-451.
[223]Schafer F Q, Buettner G R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple[J]. Free Radic Biol Med,2001,30:1191-1212.
[224]Higuchi Y. Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidativ stress[J]. Biochem Pharmacol,2003,66:1527-1535.
[225]Fang Y Z, Yang S, Wu G. Free radical, antioxidants and nutrition[J]. Nutrition,2002,18:872-879.
[226]Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. Clarendon Press,1989, Oxford.
[227]Foster K A, Galeffi F, Gerich F J, et al. Optical and pharmacological tools to investigate the rol of mitochondria during oxidative stress and neurodegeneration[J]. Prog Neurobiol,2006,79: 136-171.
[228]Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications[J]. Drug Resist Updat,2004,7:97-110.
[229]Q Zhao, X H Cao, B Zeng, et al. Musca domestica larva lectin induces apoptosis in BEL 7402 cells through a mitochondria-mediated reactive oxygen species way[J]. Biol. Pharm. Bull. 2010,33(8),1274-1278.
[230]Li Zhu, Hui Yuan, Chengzhi Guo, et al. Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3-and caspase-9-dependent mitochondrial signaling pathway[J]. Journal of Cellular Physiology,2012,227(5):1814-1820.
[231]B Antonsson. Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim, the mitochondrion[J]. Cell Tissue Res.,2001,306(3):347-361.
[232]W C Earnshaw, L M Martins, S H Kaufmann. Mammalian caspases:structure, activation, substrates, and functions during apoptosis[J]. Annu. Rev. Biochem.,1999,68:383-424.
[233]Turrens J F. Mitochondrial formation of reactive oxygen species[J]. J Physiol,2003,552:335-344.
[234]Djavaheri-Mergny M, Wietzerbin J, Besancon F, et al.2-Methoxyestradiol induces apoptosis in Ewing sarcoma cells through mitochondrial hydrogen peroxide production[J]. Oncogene,2003,22:2558-2567.
[235]Jing Wu, Li Jing, Hui Yuan, et al. T-2toxin induces apoptosis in ovarian granulosa cells of rats through reactive oxygen species-mediated mitochondrial pathway[J]. Toxicology Letters, 2011,202:168-177.
[236]Hai-Ying Yang, Yi-Mei Wang, Shuang-Qing Peng. Metallothionein-I/I I null cardiomyocytes are sensitive to Fusarium mycotoxin butenolide-induced cytotoxicity and oxidative DNA damage[J]. Toxicon,2010,55(7):1291-1296.
[237]Neha Saxena, Kausar M Ansari, Rahul Kumar, et al. Role of mitogen activated protein kinases in skin tumorigenicity of Patulin[J]. Toxicology and Applied Pharmacology,2011,257(2):264-271.
[238]Vasiliev J M, Gelfand I M. Surface changes disturbing intracellular homeostasis as a factor inducing cell growth and division[J]. Curr Mod Biol,1968,2:43-55.
[239]Missiaen L, Robberecht W, Bosch L V, et al. Abnormal intracellular Ca2+homeostasis and disease[J]. Cell calcium,2000,28:1-21
[240]Monti D M, Gesualdi N M, Matousek J, et al. The cytosolic ribonuclease inhibitor contributes to intracellular redox homeostasis[J]. FEBS Lett,2007,581:930-934.
[241]Dearborn D G, Waller R L, Brattin W J. Intracellular Ca2+homeostasis in lymphocytes from patients with mucoviscidosis[J]. Cell calcium,1984,5:306.
[242]Lange Y, Steck T L. The role of intracellular cholesterol transport in cholesterol homeostasis[J]. Trends Cell Biol,1996,6:205-208.
[243]Silver I A, Deas J, Erecinska M. Ion homeostasis in brain cells:differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience,1997,78: 589-601.
[244]Hirpara J L, Clement M V, Pervaiz S. Intracellular acidification triggered by mitochondrial-derived hydrogen peroxide is an effector mechanism for drug-induced apoptosis in tumor cells[J]. Biol Chem,2001,276:514-521.
[245]厉为良.细胞内pH、钙离子与细胞凋亡[J].国外医学·生理、病理科学与临床分册,1998,18(2)：131-134.
[246]陈松海,韩启德.细胞内游离Ca2+浓度的调节机制.生理科学进展.1993,24(1)：10-13.
[247]Dominicza A F, Bohr D F. Cell membrane abnormalites and the regulation of intracellular calcium concentration inhypertension[J]. Clin Sci,1990,79:415.
[248]Gaido M L, Cidlowski J A. Identification, purification and characterization of a calcium-dependent endonuclease(NUC18)from apoptotic rat thymocytes[J]. Biol Chem,1991,266:18580-18585.
[249]Orrenius S, Mccabe M J, Nicotera P. Ca2+-dependent mechanisms of cytotoxicity and programmed cell death[J]. Toxicol Lett,1992,64:357-364.
[250]McConkey D J, Orrenius S. The Role of Calcium in the Regulation of Apoptosis[J]. Biochem Biophys Res Commun,1997,239:357-366.
[251]Hu Q, Chang J, Tao L, et al. Endoplasmic reticulum mediated necrosis-like apoptosis of HeLacells induced by Ca2+oscillation[J]. Biochem Mol Biol,2005,38:709-716.
[252]Rekasi Z, Czompoly T, Schally A V, et al. Antagonist of growth hormone releasing hormone induces apoptosis in LNCaP human prostate cancer cells through a Ca2+-dependent pathway[J]. Proc Natl Acad Sci,2005,102:3435-3440.
[253]Grammatopoulos T N, Johnson V, Moore S A, et al. Angiotensin type 2 receptor neuroprotection against chemical hypoxia is dependent on the delayed rectifier K+channel, Na+/Ca2+exchanger and Na+/K+-ATPase in primary cortical cultures[J]. Neurosci Res,2004,50: 299-306.
[254]Altschuld R A. Intracellular calcium regulatory system during ischemia and reperfusion[J]. EXS,1996,76:87-97.
[255]Doliba N M, Doliba N M, Chang Q, et al. Mitochondrial oxidative phosphorylation in heart from stressed cardiomyopathic hamsters[J]. Mol Cell Cardiol,1999,31:543-553.
[256](?)yvind L Busk, Doreen Ndossi, Steven Verhaegen, et al. Relative quantification of the proteomic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model[J]. Toxicon,2011,58(6-7):533-542.
[257]Blaustein M P. Sodium ions, calcium ions, blood pressure regulation and hypertension: areassessment and a hypothesis[J]. Am J Physiol Cell Physiol,1977,232:C165-C173.
[258]Fujita T, Inoue H, Kitamura T, et al. Senescence marker protein-30(SMP30) rescues cell death by enhancing plasma membrane Ca2+-pumping activity in HepG2 cells[J]. Biochem Biophys Res Commun,1998,250:374-380.
[259]王启明,邹凤志,白宝璋.钙调蛋白的功能[J].农业与技术,1998,18(6)：35-36.
[260]Qin X J, Li Y N, Liang X, et al. The dysfunction of ATPases due to impaired mitochondrial respiration in phosgene-induced pulmonary edema[J]. Biochem Biophys Res Commun,2008, 367:150-155.
[261]Wang X Q, Xiao A Y, Sheline C, et al. Apoptotic insults impair Na+/K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress[J]. Cell Sci,2003,116:2099-2110.
[262]边肖海,霍静,郑曙民.细胞内酸化对宫颈癌Hela细胞凋亡的影响[J].长治医学院学报,2005,19(2)：81-83.
[263]Matsuyama S, Llopis J, Deveraux Q L, et al. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis[J]. Nat Cell Biol,2000,2:318-325.
[264]Clement M V, Ponton A, Pervaiz S. Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu[J]. FEBS Lett, 1998,440:13-18.
[265]Kerr J F, Wyllie A H, Currie A R. Apoptosis:a basis biological phenomenon with wide-ranging implications in tissue kinetics[J]. Br J Cancer,1972,26:239-257.
[266]Shi Y. Mechanism of caspase activation and inhibition during apoptosis[J]. Mol Cell.2002,9: 459-470.
[267]Yusuke Furukawa, Noriko Nishimura, Yutaka Furukawa, et al. Apaf-1 Is a Mediator of E2F-1-induced Apoptosis [J]. The Journal of Biological Chemistry,2002,277(42):39760-39768.
[268]Finkel E. The mitochondrion:is it central to apoptosis[J]. Science,2001,292:624-626.
[269]Desagher S, Martinou J C. Mitochondria as the central control point of apoptosis [J]. Trends Cell Biol,2000,10:369-377.
[270]Johnson K L, Vaillant F, Lawen A. Protein trrosine kinase inhibitors prevent didemin B induced apoptosis in HL-60 cells [J]. FEBS Lett,1996,383:1-5;
[271]Asher E, Payne C M, Bernstein C. Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy[J]. Ⅱ. Induction of non-classic apoptosis ("para-apoptosis") by tritiated thymidine [J]. Leuk Lymphoma,1995,19: 107-119。
[272]赵卫红,寿好长,闫福岭.细胞凋亡[M].郑州：河南医科大学出版社,1997,53-96.
[273]Kerr J F R, Winterford C M, Harmon B V. Apoptosis. Its significance in cancer and cancer theraph[J]. Cancer,1994,73:2013-2026;
[274]Cohen G M, Sun X M, Snowden R T, et al. Key morphological features of apoptosisy occur in the absence of internucleosomal DNA fragmentation[J]. Biochem,1992,286:331-335.
[275]James H Kouadioa, Se'bastien D Danob, Serge Moukhac, et al. Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells[J]. Toxicon,2007,49: 306-317.
[276]Zahidul Islamab, James J Pestka. LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse[J]. Toxicology and Applied Pharmacology,2006,211(1):53-63.
[277]Polyak K, Xia Y, Zweier JL, et al. A model for P53 induced apoptosis[J]. Na ture,1997,389: 300-305.
[278]Woo M, Hakem R, Soengas M S, et al. Essential contribution of Caspase-3/Cpp32 to apoptosis and its associated nuclear changes[J]. Genes Dev,1998,12:806-819.
[279]屈鸣麒,杨涛等.高压氧对颅脑损伤后神经细胞凋亡及caspase-3表达的影响[J].中华创伤杂志,2004,20(10)：613-614.
[280]Isobe N, Onodera H, Mori A, et al. Caspase-3 expression in human gastric carcinoma and its clinical significance[J]. Oncology,2004,66(3):201.
[281]Springer J E, Nottingham S A, McEwen M L, e t al. Caspase-3 apoptotic signaling following injury to the central nervous system[J]. Clin Chem Lab Med,2001,39:299-307.
[282]Budihardjo I, Oliver H, Lutter M, et al. Biochemical Pathways of Caspase Activation during Apoptosis[J]. Annu Rev Cell Dev Biol.1999,15:269-290.
[283]Ni B, Wu X, Du Y. et al. Cloning and Expression of Rat in Apoptosis of Cultured Cerebellar Granule Neurons[J]. Neurosci,1997,17(5):1561-1569.
[284]李金龙.镉致鸡脾脏淋巴细胞凋亡机理的研究[D].东北农业大学,2004.
[285]Chayma Bouaziz, Ossama Sharafel dein, Emna El Golli, et al. Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells [J]. Toxicology, 2008,254,(1-2):19-28.
[286]Antonsson B, Martinou J C. The Bcl-2 protein family[J]. Exp. Cell Res.,2000,256:50-57.
[287]Sedlak T W, Olvai Z N, Yang K, et al. Multiple Bcl-2 family members demonstrate selective dimerization with Bax[J]. Pro. Natl. Acad Sci.,1995,92:7834-7838.
[288]Hui Yuan, Youtian Deng, Liyun Yuan, et al. ynostemma pentaphyllum protects mouse male germ cells against apoptosis caused by zearalenone via Bax and Bcl-2 regulation[J]. Toxicology Mechanisms and Methods,2010,20(3):153-158.
[289]Zengli Yu, Lishi Zhang, Desheng Wu, et al. Anti-apoptotic action of zearalenone in MCF-7 cells[J]. Ecotoxicology and Environmental Safety,2005,62(3):441-446.
[290]Yanna Ma, Aihua Zhang, Zhiyu Shi, et al. A mitochondria-mediated apoptotic pathway induced by deoxynivalenol in human colon cancer cells[J]. Toxicology in Vitro,2012,26(3):414-420.
[2]陈心仪,Rebekah, Rawlings亚洲地区饲料和畜禽养殖业霉菌毒素危害实况[J].饲料广角,2008,10：39-42.
[3]王若军,苗朝华.中国饲料及饲料原料受霉菌污染的调查报告[J].饲料工业,2003,24(7)：53-54.
[4]敖志刚,陈代文.2006-2007年中国饲料及饲料原料霉菌毒素污染调查报告[J].中国畜牧兽医,2008,35(1)：152-156.
[5]张丞,刘颖莉.2008年上半年中国饲料和原料中霉菌毒素污染调查报告[J].饲料研究,2008,11：57-59.
[6]张丞,刘颖莉.2009年上半年中国饲料和原料中霉菌毒素污染情况[J].中国畜牧杂志,2009,45(16)：46-48.
[7]Hsin Yi Chen, Rebekah Rawlings亚洲地区饲料原料和配合饲料中霉菌毒素水平的调查[J].饲料研究,2008,9：28-31.
[8]吴裕本,张健.家禽生产中霉菌毒素的现状及控制[J].中国家禽,2006,28(11)：43-44.
[9]李荣涛,谢刚,付鹏程,等.小麦和玉米中玉米赤霉烯酮污染情况初探(Ⅰ)[J].2004,32(5)：36-38.
[10]邓舜洲,何庆华,章英,等.竞争间接EIASA检测饲料中脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮[J].江西农业大学学报,2006,28(2)：289-292.
[11]杨晓飞.四川地区主要饲料霉菌毒素分布规律的研究[D].四川农业大学,2007.
[12]Rotter B A, Preluskey D B, Pestka, J J. Toxicology of deoxynivalenol(vomitoxin)[J]. Toxicol, 1996,48:1-34.
[13]Ronald D Plattner, Chris M Maraagos. Determination of Deoxynivalenol and Nivalenol in Corn and Wheat by Liquid Chromatography with Electrospray Mass Spectrometry[J]. Journal of Aoac International,2003,86(1):61-65.
[14]Pestka JJ, HR Zhor, Y Moon, et al. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes:untraveling a paradox [J]. Toxicol. Lett,2004,153:61 73.
[15]Yoshizawa T, N Morooka. Trichothecenes from mold-infected cereals in Japan. In J. V. Rodricks, C. W. Hesseltine, and M. A. Mehlmen (eds.), Mycotoxins in Human and Animal Health [J]. Pathotox Publishers, Inc., Park Forest,1977:309-321.
[16]吴永宁.现代食品安全科学[M].北京：化学工业出版社,2003：310-319.
[17]Yoshizawa T, Morooka N. Studies on the toxic substances in infected cereals:Acute toxicities of new trichothecene mycotoxins:deoxynivalenol and its monoacetate [J]. J Food Hyg Soc Jpn,1974, 15:261-269.
[18]Young L G, McGirr L, Valli V E, et al. Vomitoxin in corn fed to young pigs[J]. J Anim Sci,1983, 57:655-664.
[19]Prelusky D B, Trenholm H L. The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swing[J]. Nat Toxins,1993,1:296-302.
[20]R G Rotter, B K Thompson, H L, Trenholm, et al. A prelimin ary examination of potential inter actions between deoxynivalenol (DON) and other selected Fasariummetabolites in growing pigs[J]. Canadian Journal of Animal Science,1992,72:107-116.
[21]P Pinton, J P Nougayrede, J C del Rio, et al. The food contaminant deoxynivalenol decreases intestinal barrier function and reduces claudin expression[J]. Toxicol. Appl. Pharmaco,237,2009, 41-48.
[22]M Kolf-Clauw, J Castellote, B Joly, et al. Development of a pig jejunal explant culture for studying the gastrointestinal toxicity of the mycotoxin deoxynivalenol. histopathological analysis[J]. Toxicol. In Vitro,2009,23:1580-1584.
[23]Ito E, Okusu M, Terao, et al. Light and scanning electron microscopical observations on gastrointestinal tracts injured by trichothecenes[J],1993,38:11-18.
[24]Sergeev I N, Kravchenko L V, Piliia, et al. The effect of the trichothecene mycotoxin deoxynivalenol (vomitoxin) on calcium homeostasis, vitamin D metabolism and receptors in rats[J]. Vopr Med Khim,1990,36(5):26-31.
[25]W A Awad, J Bohm, E, Razzazi-Fazeli, Effects of feeding deoxynivalenol contaminated wheat on growth performance, organ weights and histological parameters of intestine of broiler chickens[J]. Anim Physiol Anim Nutr,2006,90:32-37.
[26]W A Awad, K Ghareeb, J Bohm, et al. The impact of the fusarium toxin deoxynivalenol (DON) on poultry[J]. Int J Poult Sci,2008,7:827-842.
[27]T Sergent, M Parys, SGarsou, et al. Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations[J]. Toxico Lett, 2006,164:167-176.
[28]李群伟,侯海峰,李亚鲁等.脱氧雪腐镰刀菌烯醇致家兔多脏器损伤的实验观察[J].中国地方病防治杂志,2007,22(1)：19-22.
[29]Hara-Kudo Y, Sugita-KonishiY, Kasuga F, et al. Effects of deoxynivalenol on Salmonella enteritidis infection[J]. Mycotoxins,1996,42:51-56.
[30]Dr. Frank Iverson, Cheryl Armstrong, Eduardo Nera, et al. Chronic Feeding Study of deoxynivalenol in B6C3F1 male and female mice [J]. Teratogenesis, Carcinogenesis, and Mutagenesis.1995,15(6):283-306.
[31]Doll S, Goyarts T, Rothkotter, H J, et al. Effects of deoxynivalenol on immunohistological parameters in pigs [J]. Mycotoxin Research.2006.22(3):178-182.
[32]Tiemann U, Danicke S. In vivo and in vitro effects of the mycotoxins zearalenone and deoxynivalenol on different non-reproductive and reproductive organs in female pigs:A review [J]. Food additives and contaminants,2007,24(3):306-314.
[33]Dumitrescu G, Drinceanu D, Stef L, et al. Alteration on the histological structure of some organs induced by low levels of don mycotoxin in weaned piglets [J]. Archiva Zootechnica,2008,11(2): 12-20.
[34]Tiemann U, Brussow K P, Jonas L, et al. Effectsof diets with cereal grains contaminated by graded levels of two Fusarium toxins on selectedimmunological and histological parameters of spleeningilts[J]. Journal of Animal Science,2006,84:236-245.
[35]L F Kubena, W E Huff, R B Harvey, et al. Influence of Ochratoxin A and Deoxynivalenol on Growing Broiler Chicks[J]. Poult Sci,1988,67 (2):253-260.
[36]Moon YuSeok, Kim HyoungKab, Suh HyunHo, et al. Toxic alterations in chick embryonic liver and spleen by acute exposure to Fusarium-producing mycotoxin deoxynivalenol [J]. Biological & Pharmaceutical Bulletin,2007,30(9):1808-1812.
[37]Yan L Ouyang, Shiguang Li, James J Pestka. Effects of Vomitoxin (Deoxynivalenol) on Transcription Factor NF-κB/Rel Binding Activity in Murine EL-4 Thymoma and Primary CD4+T Cells[J]. Toxicology and Applied Pharmacology,1996,140(2):328-336.
[38]Hui-Ren Zhou, Jack R Harkema, Ding Yan, et al. Amplified proinflammatory cytokine expression and toxicity in mice coexposed to lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) [J]. Journal of Toxicology and Environmental Health, Part A:Current Issues. 1999,57(2):115-136.
[39]Thuvander A, Wilkman C, Gadhasson I. In vitro exposure of human lymphocytes to trichothecenes: individual variation in sensitivity and effects of combined exposure on lymphocyte function[J]. Food Chem Toxicol,1999,37(6):639-648.
[40]T Malovrh, B Jakovac-Strajn. Feed contaminated with toxins alter lymphocyte proliferation and apoptosis in primiparous sows during the perinatal period[J]. Food and Chemical Toxicology, 2010,48(10):2907-2912.
[41]Sun XM, Zhang XH, Wang HY, et al. Effects of sterigmatocystin, deoxynivalenol and aflatoxin G1 on apoptosis of human peripheral blood lymphocytes in vitro [J]. Biomed Environ Sci,2002, 15(2):145-152.
[42]李月红,张祥宏,王俊灵,等.脱氧雪腐镰刀菌烯醇对小鼠胸腺细胞凋亡和增殖的影响[J].中国病理生理杂志.2002,18(7)：778-781.
[43]Zahidul Islam, James J Pestka. Role of IL-1(3 in Endotoxin Potentiation of Deoxynivalenol-Induced Corticosterone Response and Leukocyte Apoptosis in Mice [J]. Toxicological Sciences, 2003,74:93-102.
[44]Pestka J J, Yan D, King L E. Flow cytom etric analysis of the effects of in vitro exposure to vomitoxin (deoxynivalenol) on apoptosis in murine T, B and IgA+ cells [J]. Food Chem Toxicol, 1994,32:1125-1136.
[45]Zhou H R, Islam Z, Pestka J J. Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol[J]. Toxicol Sci,2005,87(1):113-122.
[46]J J Pestka. Deoxynivalenol-induced IgA production and IgA nephropathy-aberrant mucosal immune response with systemic repercussions. Toxicol Lett,2003,140:287-295.
[47]T Goyarts, S Danicke, U Tiemann, et al. Effect of the Fusarium toxin deoxynivalenol (DON) on IgA, IgM and IgG concentrations and proliferation of porcine blood lymphocytes[J]. Toxicol, In Vitro,2006,20:858-867.
[48]Tanja Goyarts, Nicola Grove, Sven Danicke. Effects of the deoxynivalenol from naturally contaminated wheat given subchronically or as one single dose on the protein synthesis of peripheral blood lymphocytes and plasma proteins in the pig[J]. Food and Chemical Toxicology, 2006,44(12):1953-1965.
[49]Sandra W M van Kol, Peter J M Hendriksen, Henk van Loveren, et al. deoxynivalenol on gene expression in the murine thymus [J]. Toxicology and Applied Pharmacology,2011,250(3):299- 311.
[50]Kei-ichi Sugiyama, Masashi Muroi, Ken-ichi Tanamoto, et al. Deoxynivalenol and nivalenol inhibit lipopolysaccharide-induced nitric oxide production by mouse macrophage cells[J]. Toxicology Letters.2010,192(2):150-154.
[51]Yann J Wache, Laila Hbabi-Haddioui, Laurence Guzylack-Piriou, et al. The mycotoxin Deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages[J]. Toxicology,2009,262(3):239-244.
[52]C Banotai, D M Greene-McDowelle, J I Azcona-Olivera, et al. Effects of intermittent vomitoxin exposure on body weight, immunoglobulin levels and haematuria in the B6C3F1 mouse[J]. Food and Chemical Toxicology.1999,37(4):343-350.
[53]J I Azcona-Olivera, Y-L Ouyang, R L Warner, et al. Effects of vomitoxin (Deoxynivalenol) and cycloheximide on IL-2,4,5 and 6 secretion and mRNA levels in murine CD4+cells [J]. Food and Chemical Toxicology.1995,33(6):433-441.
[54]Hui-Ren Zhou, Ding Yan, James J Pestka. Differential Cytokine mRNA Expression in Mice after Oral Exposure to the Trichothecene Vomitoxin (Deoxynivalenol):Dose Response and Time Course[J]. Toxicology and Applied Pharmacology,1997,144(2):294-305.
[55]H R Zhou, D Yan, J J Pestka. Induction of cytokine gene expression in mice after repeated and subchronic oral exposure to vomitoxin (deoxynivalenol):differential toxin-induced hyporesponsiveness and recovery[J]. Toxicol Appl Pharmacol,1998,151:347-358.
[56]Yoshiko Sugita-Konishi. Deoxynivalenol and cycloheximide on IL-2,4,5 and 6 secretion and mRNA levels in murine CD4+ cells [J]. Food and Chemical Toxicology,1995,33(6):433-441.
[57]Z Islam, J S Gray, J J Pestka,. p38 mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes[J]. Toxicol Appl Pharmacol,2005,213:235-244.
[58]Meky F A, Haridie, L J, Evans, S W, et al. Deoxynivalenol-induced immunomodulation of human lymphocyte proliferation and cytokine production. Food and Chemical Toxicology,2001,39:827-836.
[59]Hymery N, Sibiril Y, Parent-Massin D. In vitro effects of trichothecenes on human dendritic cells. Toxicology in Vitro,2006,20(6):899-909.
[60]C J Amuzie, J R Harkema, J J Pestka. Tissue distribution and proinflammatory cytokine induction by the trichothecene deoxynivalenol in the mouse:comparison of nasal vs. oral exposure[J]. Toxicology,2008,248:39-44.
[61]C J Amuzie, J Shinozuka, J J Pestka. Induction of suppressors of cytokine signaling by the trichothecene deoxynivalenol in the mouse[J]. Toxicol Sci,2009,111:277-287.
[62]L C Borish, J W Steinke. Cytokines and chemokines[J]. Allergy Clin Immunol,2003,111:460-475.
[63]R W Johnson. Immune and endocrine regulation of food intake in sick animals[J]. Domest Anim Endocrinol,1998,15:309-319.
[64]Susanne Doll, Jan A Schrickx, Sven Danicke. Deoxynivalenol-induced cytotoxicity, cytokines and related genes in unstimulated or lipopolysaccharide stimulated primary porcine macrophages[J]. Toxicology Letters,2009,184(2):97-106.
[65]Kinser S, Jia Q S, Li M X, et al. Gene expression profiling in spleens of deoxynivalenol-exposed mice:immediate early genes as primary targets [J]. Journal of Toxicology and Environmental Health, Part A.2004,67(18):1423-1441.
[66]James J Pestka, Chidozie J Amuzie. Tissue distribution and proinflammatory cytokine gene expression following acute oral exposure todeoxynivalenol:Comparison of weanling and adult mice[J]. Food and Chemical Toxicology,2008,468(8):2826-2831.
[67]Philippe P, Francesc A, Erwan B, et al. Ingestion of deoxynivalenol(DON) contaminated feed alters the pig vaccinal immune responses [J]. Toxicology Letters,2008,177:215-222.
[68]Jacqueline Van De Walle, Beatrice Romier, Yvan Larondelle, et al. Influence of deoxynivalenol on NF-κB activation and IL-8 secretion in human intestinal Caco-2 cells[J]. Toxicology Letters, 2008,177(3):205-214.
[69]D Parent-Massin. Haematotoxicity of trichothecenes[J]. Toxicology Letters,2004,153(1):75-81.
[70]Yann J Wache, Laila Hbabi-Haddioui, Laurence Guzylack-Piriou, et al. The mycotoxin Deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages[J]. Toxicology,2009,262(3):239-244.
[71]Stefania M, Rosario R, Gluseppe B, et al. Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in J774A.1 murine macrophages[J]. Toxicology Letters,2009,189:21-26.
[72]Maika Konigs, Marlies Lenczyk, Gerald Schwerdt, et al. Cytotoxicity, metabolism and cellular uptake of the mycotoxin deoxynivalenol in human proximal tubule cells and lung fibroblasts in primary culture[J]. Toxicology,2007,240(1):48-59.
[73]Lean Mc. The phytotoxicity of Fusarium metabolites:an update since 1989[J]. Mycopathologia, 1996,133:163-179.
[74]David L Bunner, Elena R Morris. Alteration of multiple cell membrane functions in L-6 myoblasts by T-2 toxin:An important mechanism of action[J]. Toxicology and Applied Pharmacology,1988,92(1):113-121.
[75]Chang II-Moo, Mar Woong-Chon. Effect of T-2 toxin on lipid peroxidation in rats:Elevation of conjugated diene formation[J]. Toxicology Letters.1988,40(3):275-280.
[76]S K Suneja, D S Wagle, G C Ram. Effect of oral administration of T-2 toxin on glutathione shuttle enzymes, microsomal reductases and lipid peroxidation in rat liver [J]. Toxicon,1989, 27(9):995-1001.
[77]J H Kouadio, T A Mobio, I Baudrimont, et al. Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin Bl in human intestinal cell line Caco-2[]J. Toxicology,2005,213:56-65.
[78]Xiaoou Zhang, Liping Jiang, Chengyan Geng, et al. The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells[J]. Toxicon,2009,54(4):513-518.
[79]Diana Dinu, Gabriela Oana Bodea, Corina Diana Ceapa, et al. Adapted response of the antioxidant defense system to oxidative stress induced by deoxynivalenol in Hek-293 cells[J]. Toxicon,2011, 57(7):1023-1032.
[80]J M Mates. Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology[J]. Toxicology,2000,153:83-104.
[81]曹峻岭,熊咏民,张矢远,等.真菌毒素DON.T-2和NIV对培养软骨细胞作用的实验研究[J].中国地方病防治杂志,1995,10(2)：69-71.
[82]王会艳,孙旭明,张祥宏,等.脱氧雪腐镰刀菌烯醇、黄曲霉毒素G对体外培养人外周血淋巴细胞凋亡影响的研究[J].卫生研究,1999,28(2)：102-104.
[83]李斌,郭红卫.AFB1和DON对大鼠原代肝细胞DNA损伤的研究[J].中国公共卫生,2001,17(12)：1115-1116.
[84]S Knasmuller, N Bresgen, F Kassie, et al. Genotoxic effects of three Fusarium mycotoxins, fumonisin B1, moniliformin and vomitoxin in bacteria and in primary cultures of rat hepatocytes[J]. Mutat Res,1997,391:39-48.
[85]C C Hsia, J L Wu, X Q Lu, et al. Natural occurrence and clastogenic effects of nivalenol, deoxynivalenol,3-acetyl-deoxynivalenol,15-acetyldeoxynivalenol, and zearalenone in corn from a high-risk area of esophageal cancer[J]. Cancer Detect Prev,1988,13:79-86.
[86]D H Li, Y Sun, X Y Luo, et al. Genotoxicity of deoxynivalenol on CHL cells[J]. Chin J Food Hyg, 1992,4:40-43.
[87]T Frankic, T Pajk, V Rezaret al. The role of dietary nucleotides in reduction of DNA damage induced by T-2 toxin and deoxynivalenol in chicken leukocytes[J]. Food Chem Toxicol,2006,44, 1838-1844.
[88]S Bony, M Carcelen, L Olivier, et al. Genotoxicity assessment of deoxynivalenol in the Caco-2 cell line model using the comet assay[J]. Toxicol Lett,2006,166:67-76.
[89]林林,孙树秋.脱氧雪腐镰刀菌烯醇致Vero细胞核基因组DNA损伤与修复的彗星实验观察[J].中国地方病防治杂志.2004,19(3)：139-141.
[90]Hauptman K, Tichy F, Knotek Z, et al. Clincial diagnostics of hepatopathies in small mammals: Evaluation of importance of individual methods[J]. Acta Veterinaria,2001,70:297-311.
[91]Yang G, Jarvis B B, Chung Y, et al. Apoptosis induction by the satratoxins and other trichothecene mycotoxins:Relationship to ERK, p38 MAPK and SAPK/JNK Activation [J]. Toxicol Appl Pharmacol,2000,164(2):149-160.
[92]Zhou H R, Lau A S, Pestka J J. Role of Double-Stranded RNA-Activated Protein Kinase R (PKR) in Deoxynivalenol-Induced Ribotoxic Stress Response[J]. Toxicol Sci,2003,74(2):335-344.
[93]Zhou H R, Jia Q, Pestka J J. Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase Hck[J]. Toxicol Sci,2005,85(2):916-926.
[94]Zhou H R, Islam Z, Pestka J J. Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol[J]. Toxicol Sci,2005,87(1):113-122.
[95]Fatma Bensassi, Cindy Gallerne, Ossama Sharaf E1 Dein, et al. Involvement of mitochondria mediated apoptosis in deoxynivalenol cytotoxicity[J]. Food and Chemical Toxicology,2012, 50(5):1680-1689.
[96]Pestka J, Zhou H R. Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants [J]. Toxicol Sci,2006,92(2):445-455.
[97]Fatma Bensassi, Emna El Golli-Bennour, Salwa Abid-Essefi, et al. Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells[[J]. Toxicology,2009,264(1-2):104-109.
[98]O Mikami, S Yamamoto, N Yamanaka, et al. Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol[J]. Toxicology,2004,204:241-249.
[99]Stefania Marzocco, Rosario Russo, Giuseppe Bianco, et al. Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in J774A.1 murine macrophages. Toxicology Letters.2009,189(1): 21-26.
[100]Anton A Tonshina, Vera V Teplovab, Maria A Andersson, et al. The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation, oxidative phosphorylation and ion homeostasis. [J]. Toxicology,2010,276(1):49-57.
[101]彭双清,杨进生.镰刀菌毒素脱氧雪腐镰刀菌烯醇对心肌细胞Ca通道的阻滞作用[J].中国预防医学杂志.2004,5(4)：241-243.
[102]Shiguang Li, Yan L Ouyang, Wumin Dong, et al. Superinduction of IL-2 Gene Expression by Vomitoxin (Deoxynivalenol) Involves Increased mRNA Stability[J]. Toxicology and Applied Pharmacology,1997,147(2):331-342.
[103]Shu-shyan Wong, Richard C Schwartz, James J Pestka. Superinduction of TNF-a and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization [J]. Toxicology. 2001,161(1-2):139-149.
[104]Shiguang Li, Yanli Ouyanga, Gi-Hyeok Yang, et al. Modulation of Transcription Factor AP-1 Activity in Murine EL-4 Thymoma Cells by Vomitoxin (Deoxynivalenol)[J]. Toxicology and Applied Pharmacology,2000,163(1):17-25.
[105]Shu-Shyan Wong, Hui-Ren Zhou, James J Pestka. Effects Of Vomitoxin (Deoxynivalenol) On The Binding Of Transcription Factors Ap-1, Nf-Kb, And Nf-116 In Raw 264.7 Macrophage Cells[J]. Journal of Toxicology and Environmental Health, Part A:Current Issues, 2002,65(16):1161-1180.
[106]Yuseok Moon, James J Pestka. Deoxynivalenol-induced mitogen-activated protein kinase phosphorylation and IL-6 expression in mice suppressed by fish oil[J]. The Journal of Nutritional Biochemistry,2003,14(12):717-726.
[107]莫国艳,黄仁彬,林军,等.六月青萃取物对免疫抑制小鼠的影响[J]. Herald of Medicine, 2007,26(11):1264-1265.
[108]赵虎,杨在宾,杨维仁,等.日粮中添加玉米赤霉烯酮对仔猪生产性能和免疫功能影响的研究[J].山东农业大学学报(自然科学版),2009,40(4)：489-494.
[109]Jillian Calemine, Julie Zalenka, Ebru Karpuzoglu-Sahin, et al. The immune system of geriatric mice is modulated by estrogenic endocrine disruptors (diethylstilbestrol, a-zearalanol, and genistein):Effects on interferon-γ[J]. Toxicology,2003,194, (1-2):115-128
[110]Danicke S.1;Ueberschar K.-H.2;Valenta H., et al. Effects of graded levels of Fusarium-toxin-contaminated wheat in Pekin duck diets on performance, health and metabolism of deoxynivalenol and zearalenone[J]. British Poultry Science,2004,45(2):264-272.
[111]Samir Abbes, Jalila Ben Salah-Abbes, Zouhour Ouanes, et al. Preventive role of phyllosilicate clay on the Immunological and Biochemical toxicity of zearalenone in Balb/c mice [J]. International Immunopharmacology,2006,6:1251-1258.
[112]Collins T F, Sprando R L, Black T N, et al. Effects of zearalenone on in utero development in rats[J]. Food Chem Toxicol.2006,44(9):1455-1465.
[113]M. Abdelhamid, I. P. Kelad, M. M. Ali, S. A. El-Ayouty. Influence of Zearalenone on Some Metabolic, Physiological and Pathological Aspects of Female Rabbits at Two Different Ages[J]. Archiv fur Tieremaehrung,1992,42(1):63-70.
[114]Abdelhamid A M, Kelada I P., Ali M M, et al. Influence of zearalenone on some metabolic, physiological and pathological aspects of female rabbits at two different ages[J]. Archives of Animal Nutrition,1993,42(1):63-70.
[115]Obremski K, Gajecki M, Otrocka-Domagaa I, et al. Clinical case of rabbit zearalenone mycotoxicosis[J]. Medycyna Weterynaryjna,2005,61(4):458-461.
[116]Popova-Ralcheva S, Gudev D, Yanchev I, et al. Effect of the mycotoxins zearalenone and aflatoxin B1 on some biochemical indices, internal organs and glands in chicks. II. Possibilities to antagonize their effect by Cleanotox. [J]. Zhivotnov'dni Nauki,2003,40(3-4):100-104.
[117]Andretta, I., Lovatto, P. A., Hauschild, L, et al. Feeding of pre-pubertal gilts with diets containing zearalenone[J]. Arquivo Brasileiro de Medicina Veterinaria e Zootecnia,2008,60(5): 1227-1233.
[118]M. L. Biehl, D. B. Prelusky, G. D. Koritz, K. E. Hartin, W. B. Buck, H. L. Trenholm. Biliary Excretion and Enterohepatic Cycling of Zearalenone in Immature Pigs[J]. Toxicology and Applied Pharmacology,1993,121(1):152-159.
[119]赵虎,杨在宾,杨维仁,等.玉米赤霉烯酮对仔猪生产性能和内脏器官发育影响的研究[J].粮食与饲料工业.2008,10：37-38
[120]M. Dong, X. J. He, P. Tulayakul, et al. The toxic effects and fate of intravenously administered zearalenone in goats [J]. Toxicon,2010,55(2-3):523-530.
[121]钱利纯,罗兆正.ZEA对畜禽的毒害作用研究进展[J].黑龙江畜牧兽医,2005,9：78-80.
[122]Pestka J J, Tai J H, Witt M F, et al. Suppression of immune response in the B6C3F1 mouse after dietary exposure to the fusarium mycotoxins deoxynivalenol(vomitoxin) and zearalenone[J]. Food Chem Toxic,1987,25;297-304
[123]Vlata Z, Porichis F, Tzanakakis G, et al. A study of zearalenone cytotoxicity on human peripheral blood mononu clear cells[J]. Toxicol Lett,2006,165(3):274-281.
[124]梁梓森,许利娜,马勇江等.玉米赤霉烯酮对小鼠胞腺细胞凋亡的影响[J].中国兽医杂志.2009,45(7)；88-90
[125]Lioi MB, Santoro A, Barbieri R, et al. Ochratoxin and zearalenone;a comparative study on genotoxic effects and cell death induced in bovine lymphocytes [J]. Mutation Research.2004. 557;19-24.
[126]Berek L, Petri I B, Mesterhazy A, et al. Effects of mycotoxins on human immune functionsin vitroolToxicologyin Vitro,2001,15:25-30
[127]Speranda Marcela, Liker B, Sperand T, et al. Haematological and biochemical parameters of weaned piglets fed on fodder mixture contaminated by zearalenone with addition of clinoptilolite [J]. Acta Veterinaria (Beograd),2006,56(2-3):121-136.
[128]马勇江,许利娜,李玉谷,等.玉米赤霉烯酮对小鼠脾淋巴细胞凋亡的影响[J].家畜生态学报.2009,30(1)；52-56.
[129]Forsell, Pestka. Relation of 8-ketotrichothecene and zearalenone analog structure to inhibition of mitogen-induced human lymphocyte blastogenesis [J]. Appl. Environ. Microbiol, 1985,50:1304-1307
[130]Marin M L, Murtha J, Dong W, et al. Effects of mycotoxins on cytokine production and proliferation in EL-4 thymoma cells[J]. Journal of Toxicol Environ Health,1996,48:379-396.
[131]Eriksen G S, Alexander J. Fusatium toxins in cereals-a risk assessment [A]. Nordic Council of Ministers[C]. Tema Nord Copenhagen,1998.502;7-58
[132]Murata H, Sultana P, Shimada N, et al. Structure activity relationships among zearalenone and its derivatives based on bovine neutrophil chemiluminescence. Vet Hum Toxicol,2003,45,18-20.
[133]Daniela E. Marin, Ionelia Taranu, Radu Burlacu, et al. Effects of zearalenone and its derivatives on the innate immune response of swine[J]. Toxicon,2010,56(6):956-963.
[134]范小龙,刘长永,剡海阔,等.玉米赤霉烯酮对小鼠脾淋巴细胞增殖及分泌细胞因子的 影响.中国畜牧兽医,2011,38(5)：48-54.
[135]Pestka J, Zhou H R. Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants [J]. Toxicol Sci,2006,92(2):445-455.
[136]Conkova E, Laciakova A, Pastorova B, et al. The effect of zearalenone on some enzymatic parameters in rabbits [J]. Toxicol Lett,2001,121;145-149.
[137]Maaroufi K, Chekir L, Creppy E E, et al. Zearalenone induces modifications of haematological and biochemical parameters in rats[J]. Toxicon,1996,34;535-540.
[138]Minervini F, Dell' Aquila M. E., Maritato F, et al., Toxic effects of the mycotoxin zearalenone and its derivatives on in vitro maturation of bovine oocytes and 17β-estradiol levels in mural granulosa cell cultures[J]. Toxicology in Vitro,2001,15:489-495.
[139]Trevor K., Diaz S. G., and Swamy H. V. L. N. Current concepts in mycotoxicoses in swing. In:Duarte Diaz, (Eds), The mycotoxin blue book. Nottingham University Press,2004:239-240.
[140]Aim H, Greising T, Brussow K. P., et al. The influence of the mycotoxins deoxynivalenol and zearalenol on in vitro maturation of pig oocytes and in vitro culture of pig zygotes[J]. Toxicology in Vitro,2002,16:43-48.
[141]Aim H., Brussowa K. P., Tomer H., et al. Influence of Fusarium-toxin contaminated feed on initial qulity and meiotic competence of gilt oocytes[J]. Reproductive Toxicology,2006,22:44-50.
[142]I. A. Tsakmakidis, A. G. Lymberopoulos, C. Alexopoulos, et al. In vitro effect of zearalenone and α-zearalenol in boar sperm characteristics and acrosome reaction[J]. Reprod. Domest. Anim.,2006,41:394-401.
[143]Kuiper G G J M, Lemmen J G, Carlsson B. Interaction of estrogenic chemical and phytostrogens with estrogen receptor [J]. Endocrinolgy,1998,139:4252-4263.
[144]Dees C, Foster J S, Ahamed S. Dietary estrogens stimulate human breast cells to enter the cell cycle [J]. Environ Health Perspect,1997,105(suppl 3):633-636;
[145]Sheehan D M, Branham W S, Medlock KL. Estrogenic activity of zearalenone and zearalanol in the neonatal rat uterus [J]. Teratology,1984,29:383-392
[146]Olsen M, Petterson H, Kiessling KH. Reduction of zearalenone to zearalenol in female rat liver by 3-hydroxysteroid dehydrogenase[J]. Acta Pharmacol Et Toxicol,1986(48):157-161.
[147]James H K, Theophile A M, Isabelle B, et al. Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2 [J]. Toxicology,2005,213:56-65.
[148]E. Ferrer, A. Juan-Garcia, G Font, et al. Reactive oxygen species induced by beauvericin, patulin and zearalenone in CHO-K1 cells. [J]. Toxicology in Vitro,2009,23(8):1504-1509.
[149]Quane Z, Abid S, Ayed I, et al. Induction of micronulei by zearalenone in vero monkey kidney cells and in bone marrow cells of mice;protective effect of vitamin E [J]. Mutat Res,2003, 538:63-70.
[150]Abid-Essefi S, Ouanes Z, Hassen W, et al. Cytotoxicity, inhibition of DNA and protein syntheses and oxidative damage in cultured cells exposed to zearalenone[J]. Toxicology in Vitro, 2004.18:467-474.
[151]J Y Yang, G X Wang, J. L. Liu, et al. Toxic effects of zearalenone and its derivatives a zearalenol on male reproductive system in mice[J]. Reprod Toxicol,2007,24:381-387.
[152]I Ayed-Boussema, Z Ouanes, H Bacha, et al. Toxicities induced in cultured cells exposed to zearalenone:apoptosis or mutagenesis?[J]. Biochem Mol Toxicol,2007,21:136-144.
[153]E El-Golli, W Hassen, A Bouslimi, et al. Induction of Hsp70 in Vero cells in response to mycotoxins cytoprotection by sub-lethal heat shock and by vitamin E[J]. Toxicol Lett,2006,16: 122-130.
[154]B E El-Golli, C. Bouaziz, M. Ladjimi, et al. Comparative mechanisms of zearalenone and ochratoxin A toxicities on cultured HepG2 cells:in oxidative stress a common process[J]. Environ Toxicol,2009,24:538-548.
[155]E Benzoni, F Minervini, A. Giannoccaro, et al. Influence of in vitro exposure to mycotoxin zearalenone and its derivatives on swine sperm quality[J]. Reprod Toxicol,2008,25:461-467.
[156]I A Tsakmakidis, A G Lymberopoulos, T. A. A. Khalifa, et al. Evaluation of zearalenone and a-zearalenol toxicity on boar sperm DNA integrity[J]. Appl. Toxicol,2008,28,681-688.
[157]Wafa Hassen, Imen Ayed-Boussema, Amaia Azqueta Oscoz, et al. The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells:Oxidative DNA damage, gluthatione depletion and stress proteins induction[J]. Toxicology,2007,232(3):294-302
[158]Zouhour Ouanes-Ben Othmen, Emna El Golli, Salwa Abid-Essefi, et al. Cytotoxicity effects induced by Zearalenone metabolites, a Zearalenol and β Zearalenol, on cultured Vero cells [J]. Toxicology,2008,252(1-3):72-77
[159]郭炳虹,张佳颖.F-2毒素致DNA损伤研究[J].黑龙江医学,2004,28(3)：193-194.
[160]Quanes Z, Aved-Boussema, Baati T, et al. Zearalenone induces chromosome aberrations in mouse bone marrow:preventive effect of 17beta-estradiol, progesterone and vitamin E[J]. Mutat Res,2005,565 (2):139-149.
[161]孙美乐,王博文.玉米赤霉烯酮对体外培养大鼠肝细胞的影响[J]中国地方病防治杂志,1997,2：69-70.
[162]严继承,郑一凡,曾群力,等.玉米赤霉烯酮对细胞间隙连接通讯的影响[J].卫生毒理学杂志,2004,18(3)：160-162.
[163]邓友田,袁慧.玉米赤霉烯酮毒性机理研究进展[J].动物医学进展,2007,28(2)：89-92.
[164]Yosra Ayed, Imen Ayed-Boussema, Zouhour Ouanes, et al. In vitro and in vivo induction of chromosome aberrations by alpha-and beta-zearalenols:Comparison with zearalenone[J]. Mutation Research/Genetic Toxicology and Environmental Mutagenesis,2011,726(1):42-46.
[165]F Minervini, G M Lacalandra, A Filannino, et al. Effects of in vitro exposure to natural levels of zearalenone and its derivatives on chromatin structure stability in equine spermatozoa[J]. Theriogenology,2010,73:392-403.
[166]Abid-Essefi S, Baudrimont I, Hassen W, et al. DNA fragmentation, apoptosis and cell cycle arrest induced by zearalenone in cultured DOK, Vero and Caco-2 cells;prevention by Vitamin E[J]. Toxicology,2003,192;237-248.
[167]S Abid-Essefi, C Bouaziz, E E Golli-Bennour, et al. Comparative study of toxic effects of zearalenone, and its two major metabolites alpha-zearalenol and beta-zearalenol on cultured human Caco-2 cells[J]. Biochem. Mol. Toxicol.,2009,23,233-243.
[168]Kim I H, Son H Y, Cho S W, et al. Zearalenone induces male germ cell apoptosis in rats[J]. Toxicol Lett.2003,138(3):185-192.
[169]余增丽,张立实,吴德生.玉米赤霉烯酮对乳腺癌细胞MCF-7增殖和凋亡的影响[J].中国预防医学杂志,2005,39(5)：328-331.
[170]U Tiemann, T Viergutza, L Jonasb, et al. Influence of the mycotoxins α-and β-zearalenol and deoxynivalenol on the cell cycle of cultured porcine endometrial cells[J]. Reproductive Toxicology,2003,17(2):209-218.
[171]符达.玉米赤霉烯酮对SD大鼠卵巢p53第八外显子突变的研究[D].湖南农业大学硕士论文2005.
[172]曹林枝.p53基因及其分子生物学作用[J].中国临床医药,2003,5(1)；77-80.
[173]Ji-Yeon Yu, Zhong-Hua Zhenga, Young-Ok Son, et al. Mycotoxin zearalenone induces AIF-and ROS-mediated cell death through p53-and MAPK-dependent signaling pathways in RAW264.7 macrophages [J]. Toxicology in Vitro,2011,25(8):1654-1663
[174]H L Trenholm, B K Thompson, B C Foster, et al. Effects of feeding diets containing Fusarium (naturally) contaminated wheat or pure deoxynivalenol (DON) in growing pigs[J]. Canadian Journal of Animal Science,1994,74(2):361-369.
[175]G J A Speijers, M H M Speijers. Combined toxic effects of mycotoxins[J]. Toxicology Letters,2004,153:91-98.
[176]K C Williams, B J Blaney, R T Peters. Pigs fed Fusarium-infected maize containing zearalenone and nivalenol with sweeteners and bentonite[J]. Livestock Production Science,1994, 39(3):275-281.
[177]Trenholm H L, Friend D W, Thompson, et al. Effects of zearalenone and deoxynivalenol combinations fed to pigs[J]. Pro Jpn Assoc Mycotox,1988, Suppll:101-102.
[178]H V L N Swamy, T K Smith, E J MacDonald. Effects of feeding blends of grains naturally contaminated with mycotoxins Fusarium on brain regional neurochemistry of starter pigs and broiler chickens[J]. Journal Of Animal Science,2004,82:2131-2139.
[179]Danicke S, Brussow K P, Goyarts T, et al. On the transfer of the Fusarium toxins deoxynivalenol(DON) and zearalenone (ZEA) from the sow to the full-term piglet during the last third of gestation [J]. Food & Chemical Toxicology,2007,45(9):1565-1574.
[180]Tiemann U, BrussowK P, Kuchenmeister U, et al. Changes in the spleen and liver of pregnant sows and full-term piglets after feeding diets naturally contaminated with deoxynivalenol and zearalenone [J]. Veterinary Journal,2008,176:188-196.
[181]Tiemann U, Brussow K P, Dannenberger D, et al. The effect of feeding a diet naturally contaminated with deoxynivalenol (DON) and zearalenone (ZON) on the spleen and liver of sow fetus from day 35 to 70 of gestation [J]. Toxicology letters,2008,179(3):113-117.
[182]Chen Feng, Ma YuLin, Xue ChunYi, et al. The combination of deoxynivalenol and zearalenone at permitted feed concentrations causes serious physiological effects in young pigs[J]. Journal of Veterinary Science,2008,9(1):39-44.
[183]苏军.镰刀菌毒素对猪的抗营养效应及其机制研究.[硕士学位论文].雅安：四川农业大学,2008.
[184]Yegani M, Smith T K, Leeson S, et al. Effects of Feeding Grains Naturally Contaminated with Fusarium Mycotoxins on Performance and Metabolism of Broiler Breeders[J]. Poultry science,2006,85(9):1541-1549.
[185]T K Smith. Contemporary concepts in the aetiology and prevention of mycotoxicoses in livestock and poultry[J]. The mycotoxins factbook:Food and Feed topics,2006:313-326.
[186]Danicke S, Ueberschar K-H, Halle I, et al. Effect of addition of a detoxifying agent to laying hen diets containing uncontaminated or Fusarium toxin-contaminated maize on performance of hens and on carryover of zearalenone[J]. Poul Sci,2002,81:1671-1680.
[187]M Levkut, V Revajova, Z Slaminkova, et, al. Lymphocyte subpopulations in blood and duodenal epithelium of broilers fed diets contaminated with deoxynivalenol and zearalenonefj]. Animal Feed Science and Technology,2011,165(3-4):210-217.
[188]Boeira L S, Bryce J H, Stewart G G, et, al. The effect of combination of Fusarium mycotoxins (deoxynivalenol, zearalenone and fumonisin B1)on growth of brewing yeasts[J]. J Appl Microbiol, 2000,88:388-403.
[189]Coppock R W, Mostrom M S, Sparling C G, et, al. Apparent zearalenone intoxication in a dairy herd from feeding spoiled acid-treated corn[J]. Veterinary and Human Toxicology,1990, 32(3):246-248.
[190]James H Kouadioa, Se'bastien D Danob, Serge Moukhac, et al. Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells[J]. Toxicon,2007,49: 306-317.
[191]Abdelhamid A M. Effect of feeding rabbits on naturally moulded and mycotoxin contaminated diet[J]. Archives of Animal Nutrition,1990,40(1-2):55-63.
[192]H A C Atkinson, K Miller. Inhibitory effect of deoxynivalenol,3-acetyldeoxynivalenol and zearalenone on induction of rat and human lymphocyte proliferation[J]. Toxicology Letters,1984, 23(2):215-221.
[193]Shinya Nagafuji, Hikaru Okabe, Hiroshige Akahane, et, al. Trypanocidal constituents in plants 4. withanolides from the aerial parts of physalis angulata[J]. Biological and Pharmaceutical Bulletin,2004,27(2):193-197.
[194]张诚,陈幸华,张曦等.WST-8检测培养小鼠脾NK细胞增殖及杀伤活性的研究.西南国防医药,2008,18(3)：313-315.
[195]Okamura M, Lillehoj H S, Raybourne R B, et, al. Cell-mediated immune responses to a killed Salmonella enteritidis vaccine:lymphocyte proliferation, T-cell changes and interleukin-6(IL-6), IL-1, IL-2, and IFN-γ production[J]. Comp Immun Microbiol Infect Dis,2004,27: 255-272.
[196]K Miller, H A C Atkinson. The In vitro effects of trichothecenes on the immune system[J]. Food and Chemical Toxicology,1986,24(6-7):545-549.
[197]Vermes I, Haanen C, Steffens-Nakken H, et, al. A novel assay for apoptosis, flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein-labeled[J]. Annexin V J Immunol Meth,1995,184:39-51.
[198]Gunnar Sundst(?)l Eriksen, Hans Pettersson. Toxicological evaluation of trichothecenes in animal feed[J] Animal Feed Science and Technology,2004,114(1-4):205-239.
[199]Y Cetin, L B Bullerman. Cytotoxicity of Fusarium mycotoxins to mammalian cell cultures as determined by the MTT bioassay[J]. Food and Chemical Toxicology,2005,43(5):755-764.
[200]韩贻仁.分子细胞生物学[M].北京：科学出版社,2003：648-661.
[201]Shabani A, Rabbani A. Lead nitrate induced apoptosis in alveolar macrophages from rat lung[J]. Toxicology,2000,149:109-114.
[202]H De La Fuente, D Portales-Perez, L Baranda, et al. Effect of arsenic, cadmium and lead on the induction of apoptosis of normal human mononuclear cells[J] Clinical & Experimental Immunology,2002,129(1):69-77.
[203]夏世钧,吴中亮.分子毒理学基础[M].武汉：湖北科学技术出版社,2001：87-90.
[204]Trevor F Slater. Free-radical mechanisms in tissue injury[J]. Biochem,1984,222:1-15.
[205]Tanusree Sen, Nikantha Sen, Gayatri Tripathi, Chatterjee Uttara, Sasanka Chakrabarti. Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria[J]. Neurochem Int,2006,49:20-27.
[206]Etsuo Niki, Yasukazu Yoshida, Yoshiro Saito, Noriko Noguchi. Lipid peroxidation: mechanism, inhibition, and biological effects[J]. Biochemical and Biophysical Resarch Communications,2005,338:668-676.
[207]Koji Uchida.4-Hydroxy-2-nonenal:a product and mediator of oxidative stress. Progress in Lipid Research,2003,42(4):318-343.
[208]Jian Luo, Riyi Shi. Acroline induced oxidative stress in brain mitochondria[J]. Neurochemistry Interational,2005,46:243-252.
[209]I Ayed-Boussema, C Bouaziz, K Rjiba, et al. The mycotoxin zearalenone induces apoptosis in human hepatocytes (HepG2) via p53-dependent mitochondrial signalling pathway[J]. Toxicology In Vitro,2008,22:1671-1680.
[210]C Bouaziz, O Sharafeldein, E El Golli, et al. Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells[J]. Toxicology,2008,254: 19-28.
[211]Pathak N, Khandelwal S. Influence of cadmium on murine thymocytes:potentiation of apoptosis and oxidative stress[J]. Toxicol Lett,2006,165:121-132.
[212]Scaduto R C, Grotyohann L W. Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J,1999,76:469-477.
[213]Dimri U, Ranjan R, Kumar N, et al. Changes in oxidative stress indices, zinc and copper concentrations in blood in canine demodicosis[J]. Vet Parasitol,2008,154:98-102.
[214]Huxtable R J. Physiological action of taurine[J]. Physiol Revi,1992,72:101-142.
[215]Kelly S A, Havrilla C M, Brady T C, et al. Oxidative stress in toxicology:established mammalian and emerging piscine model systems[J]. Environ Health Perspect,1998,106:375-384.
[216]Findel T, Holbrook N J. Oxidants, oxidative stress and the bilolgy of aging[J]. Nature,2000, 408:239-247.
[217]Bird R P, Draper H H, Effect of malondialdehyde acetaldehyde on cultured mammalian cells: growth, morphology and synthesis of macromolecules[J]. Journal of Toxicology and Environmental Health.1980,6:811-823.
[218]Tomita M, Okuyama T. Determination of malondialdehyde in oxidized biological materials by high-performance liquid chromatography[J].1990,515:391-397.
[219]Pexter D T, Sian J, Rose S, et al. Indices of oxidative stress and mito-chondrial function in individiulas with incidental lewy body disease[J]. Ann Neurol,1994,35:38-44.
[220]Kehrer J P, Mossman B T, Sevanian A, et al. Free radical mechanisms in chemical pathogenesis[J]. Toxicol and Applied Phanrmacol,1998,95:349-356.
[221]Larsen M, Webb G, Kennington S, et al. Mannitol in cardioplegia as an oxygen free radical scavenger measyred by malondialdehyde[J]. Perfusion,2002,17(1):51-55.
[222]Sies H, Akerboom T P. Glutathione disulfide(GSSG)efflux from cells and tissues[J]. Method Enzymol,1984,105:445-451.
[223]Schafer F Q, Buettner G R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple[J]. Free Radic Biol Med,2001,30:1191-1212.
[224]Higuchi Y. Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidativ stress[J]. Biochem Pharmacol,2003,66:1527-1535.
[225]Fang Y Z, Yang S, Wu G. Free radical, antioxidants and nutrition[J]. Nutrition,2002,18:872-879.
[226]Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. Clarendon Press,1989, Oxford.
[227]Foster K A, Galeffi F, Gerich F J, et al. Optical and pharmacological tools to investigate the rol of mitochondria during oxidative stress and neurodegeneration[J]. Prog Neurobiol,2006,79: 136-171.
[228]Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications[J]. Drug Resist Updat,2004,7:97-110.
[229]Q Zhao, X H Cao, B Zeng, et al. Musca domestica larva lectin induces apoptosis in BEL 7402 cells through a mitochondria-mediated reactive oxygen species way[J]. Biol. Pharm. Bull. 2010,33(8),1274-1278.
[230]Li Zhu, Hui Yuan, Chengzhi Guo, et al. Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3-and caspase-9-dependent mitochondrial signaling pathway[J]. Journal of Cellular Physiology,2012,227(5):1814-1820.
[231]B Antonsson. Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim, the mitochondrion[J]. Cell Tissue Res.,2001,306(3):347-361.
[232]W C Earnshaw, L M Martins, S H Kaufmann. Mammalian caspases:structure, activation, substrates, and functions during apoptosis[J]. Annu. Rev. Biochem.,1999,68:383-424.
[233]Turrens J F. Mitochondrial formation of reactive oxygen species[J]. J Physiol,2003,552:335-344.
[234]Djavaheri-Mergny M, Wietzerbin J, Besancon F, et al.2-Methoxyestradiol induces apoptosis in Ewing sarcoma cells through mitochondrial hydrogen peroxide production[J]. Oncogene,2003,22:2558-2567.
[235]Jing Wu, Li Jing, Hui Yuan, et al. T-2toxin induces apoptosis in ovarian granulosa cells of rats through reactive oxygen species-mediated mitochondrial pathway[J]. Toxicology Letters, 2011,202:168-177.
[236]Hai-Ying Yang, Yi-Mei Wang, Shuang-Qing Peng. Metallothionein-I/I I null cardiomyocytes are sensitive to Fusarium mycotoxin butenolide-induced cytotoxicity and oxidative DNA damage[J]. Toxicon,2010,55(7):1291-1296.
[237]Neha Saxena, Kausar M Ansari, Rahul Kumar, et al. Role of mitogen activated protein kinases in skin tumorigenicity of Patulin[J]. Toxicology and Applied Pharmacology,2011,257(2):264-271.
[238]Vasiliev J M, Gelfand I M. Surface changes disturbing intracellular homeostasis as a factor inducing cell growth and division[J]. Curr Mod Biol,1968,2:43-55.
[239]Missiaen L, Robberecht W, Bosch L V, et al. Abnormal intracellular Ca2+homeostasis and disease[J]. Cell calcium,2000,28:1-21
[240]Monti D M, Gesualdi N M, Matousek J, et al. The cytosolic ribonuclease inhibitor contributes to intracellular redox homeostasis[J]. FEBS Lett,2007,581:930-934.
[241]Dearborn D G, Waller R L, Brattin W J. Intracellular Ca2+homeostasis in lymphocytes from patients with mucoviscidosis[J]. Cell calcium,1984,5:306.
[242]Lange Y, Steck T L. The role of intracellular cholesterol transport in cholesterol homeostasis[J]. Trends Cell Biol,1996,6:205-208.
[243]Silver I A, Deas J, Erecinska M. Ion homeostasis in brain cells:differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience,1997,78: 589-601.
[244]Hirpara J L, Clement M V, Pervaiz S. Intracellular acidification triggered by mitochondrial-derived hydrogen peroxide is an effector mechanism for drug-induced apoptosis in tumor cells[J]. Biol Chem,2001,276:514-521.
[245]厉为良.细胞内pH、钙离子与细胞凋亡[J].国外医学·生理、病理科学与临床分册,1998,18(2)：131-134.
[246]陈松海,韩启德.细胞内游离Ca2+浓度的调节机制.生理科学进展.1993,24(1)：10-13.
[247]Dominicza A F, Bohr D F. Cell membrane abnormalites and the regulation of intracellular calcium concentration inhypertension[J]. Clin Sci,1990,79:415.
[248]Gaido M L, Cidlowski J A. Identification, purification and characterization of a calcium-dependent endonuclease(NUC18)from apoptotic rat thymocytes[J]. Biol Chem,1991,266:18580-18585.
[249]Orrenius S, Mccabe M J, Nicotera P. Ca2+-dependent mechanisms of cytotoxicity and programmed cell death[J]. Toxicol Lett,1992,64:357-364.
[250]McConkey D J, Orrenius S. The Role of Calcium in the Regulation of Apoptosis[J]. Biochem Biophys Res Commun,1997,239:357-366.
[251]Hu Q, Chang J, Tao L, et al. Endoplasmic reticulum mediated necrosis-like apoptosis of HeLacells induced by Ca2+oscillation[J]. Biochem Mol Biol,2005,38:709-716.
[252]Rekasi Z, Czompoly T, Schally A V, et al. Antagonist of growth hormone releasing hormone induces apoptosis in LNCaP human prostate cancer cells through a Ca2+-dependent pathway[J]. Proc Natl Acad Sci,2005,102:3435-3440.
[253]Grammatopoulos T N, Johnson V, Moore S A, et al. Angiotensin type 2 receptor neuroprotection against chemical hypoxia is dependent on the delayed rectifier K+channel, Na+/Ca2+exchanger and Na+/K+-ATPase in primary cortical cultures[J]. Neurosci Res,2004,50: 299-306.
[254]Altschuld R A. Intracellular calcium regulatory system during ischemia and reperfusion[J]. EXS,1996,76:87-97.
[255]Doliba N M, Doliba N M, Chang Q, et al. Mitochondrial oxidative phosphorylation in heart from stressed cardiomyopathic hamsters[J]. Mol Cell Cardiol,1999,31:543-553.
[256](?)yvind L Busk, Doreen Ndossi, Steven Verhaegen, et al. Relative quantification of the proteomic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model[J]. Toxicon,2011,58(6-7):533-542.
[257]Blaustein M P. Sodium ions, calcium ions, blood pressure regulation and hypertension: areassessment and a hypothesis[J]. Am J Physiol Cell Physiol,1977,232:C165-C173.
[258]Fujita T, Inoue H, Kitamura T, et al. Senescence marker protein-30(SMP30) rescues cell death by enhancing plasma membrane Ca2+-pumping activity in HepG2 cells[J]. Biochem Biophys Res Commun,1998,250:374-380.
[259]王启明,邹凤志,白宝璋.钙调蛋白的功能[J].农业与技术,1998,18(6)：35-36.
[260]Qin X J, Li Y N, Liang X, et al. The dysfunction of ATPases due to impaired mitochondrial respiration in phosgene-induced pulmonary edema[J]. Biochem Biophys Res Commun,2008, 367:150-155.
[261]Wang X Q, Xiao A Y, Sheline C, et al. Apoptotic insults impair Na+/K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress[J]. Cell Sci,2003,116:2099-2110.
[262]边肖海,霍静,郑曙民.细胞内酸化对宫颈癌Hela细胞凋亡的影响[J].长治医学院学报,2005,19(2)：81-83.
[263]Matsuyama S, Llopis J, Deveraux Q L, et al. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis[J]. Nat Cell Biol,2000,2:318-325.
[264]Clement M V, Ponton A, Pervaiz S. Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu[J]. FEBS Lett, 1998,440:13-18.
[265]Kerr J F, Wyllie A H, Currie A R. Apoptosis:a basis biological phenomenon with wide-ranging implications in tissue kinetics[J]. Br J Cancer,1972,26:239-257.
[266]Shi Y. Mechanism of caspase activation and inhibition during apoptosis[J]. Mol Cell.2002,9: 459-470.
[267]Yusuke Furukawa, Noriko Nishimura, Yutaka Furukawa, et al. Apaf-1 Is a Mediator of E2F-1-induced Apoptosis [J]. The Journal of Biological Chemistry,2002,277(42):39760-39768.
[268]Finkel E. The mitochondrion:is it central to apoptosis[J]. Science,2001,292:624-626.
[269]Desagher S, Martinou J C. Mitochondria as the central control point of apoptosis [J]. Trends Cell Biol,2000,10:369-377.
[270]Johnson K L, Vaillant F, Lawen A. Protein trrosine kinase inhibitors prevent didemin B induced apoptosis in HL-60 cells [J]. FEBS Lett,1996,383:1-5;
[271]Asher E, Payne C M, Bernstein C. Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy[J]. Ⅱ. Induction of non-classic apoptosis ("para-apoptosis") by tritiated thymidine [J]. Leuk Lymphoma,1995,19: 107-119。
[272]赵卫红,寿好长,闫福岭.细胞凋亡[M].郑州：河南医科大学出版社,1997,53-96.
[273]Kerr J F R, Winterford C M, Harmon B V. Apoptosis. Its significance in cancer and cancer theraph[J]. Cancer,1994,73:2013-2026;
[274]Cohen G M, Sun X M, Snowden R T, et al. Key morphological features of apoptosisy occur in the absence of internucleosomal DNA fragmentation[J]. Biochem,1992,286:331-335.
[275]James H Kouadioa, Se'bastien D Danob, Serge Moukhac, et al. Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells[J]. Toxicon,2007,49: 306-317.
[276]Zahidul Islamab, James J Pestka. LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse[J]. Toxicology and Applied Pharmacology,2006,211(1):53-63.
[277]Polyak K, Xia Y, Zweier JL, et al. A model for P53 induced apoptosis[J]. Na ture,1997,389: 300-305.
[278]Woo M, Hakem R, Soengas M S, et al. Essential contribution of Caspase-3/Cpp32 to apoptosis and its associated nuclear changes[J]. Genes Dev,1998,12:806-819.
[279]屈鸣麒,杨涛等.高压氧对颅脑损伤后神经细胞凋亡及caspase-3表达的影响[J].中华创伤杂志,2004,20(10)：613-614.
[280]Isobe N, Onodera H, Mori A, et al. Caspase-3 expression in human gastric carcinoma and its clinical significance[J]. Oncology,2004,66(3):201.
[281]Springer J E, Nottingham S A, McEwen M L, e t al. Caspase-3 apoptotic signaling following injury to the central nervous system[J]. Clin Chem Lab Med,2001,39:299-307.
[282]Budihardjo I, Oliver H, Lutter M, et al. Biochemical Pathways of Caspase Activation during Apoptosis[J]. Annu Rev Cell Dev Biol.1999,15:269-290.
[283]Ni B, Wu X, Du Y. et al. Cloning and Expression of Rat in Apoptosis of Cultured Cerebellar Granule Neurons[J]. Neurosci,1997,17(5):1561-1569.
[284]李金龙.镉致鸡脾脏淋巴细胞凋亡机理的研究[D].东北农业大学,2004.
[285]Chayma Bouaziz, Ossama Sharafel dein, Emna El Golli, et al. Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells [J]. Toxicology, 2008,254,(1-2):19-28.
[286]Antonsson B, Martinou J C. The Bcl-2 protein family[J]. Exp. Cell Res.,2000,256:50-57.
[287]Sedlak T W, Olvai Z N, Yang K, et al. Multiple Bcl-2 family members demonstrate selective dimerization with Bax[J]. Pro. Natl. Acad Sci.,1995,92:7834-7838.
[288]Hui Yuan, Youtian Deng, Liyun Yuan, et al. ynostemma pentaphyllum protects mouse male germ cells against apoptosis caused by zearalenone via Bax and Bcl-2 regulation[J]. Toxicology Mechanisms and Methods,2010,20(3):153-158.
[289]Zengli Yu, Lishi Zhang, Desheng Wu, et al. Anti-apoptotic action of zearalenone in MCF-7 cells[J]. Ecotoxicology and Environmental Safety,2005,62(3):441-446.
[290]Yanna Ma, Aihua Zhang, Zhiyu Shi, et al. A mitochondria-mediated apoptotic pathway induced by deoxynivalenol in human colon cancer cells[J]. Toxicology in Vitro,2012,26(3):414-420.