镉致大鼠亚慢性损伤与ERCC1基因表达变化的研究
摘要
1.目的
镉(Cadmium,Cd)及其化合物是常见的工业毒物和环境污物,进入机体内的镉可引起多种组织器官的损害,甚至导致肿瘤的发生。根据国际癌症研究组织(IARC)的报告,镉及其化合物是确认的第一类致癌物,是人类危害最大的金属毒物之一。因此,镉暴露及其健康损害,特别是镉低水平长期毒作用已经成为毒理学研究的热点,其中关于DNA修复基因在亚慢性镉暴露动物体内的表达变化鲜见报道。本实验通过创建大鼠亚慢性镉暴露模型,对镉低水平较长期致大鼠的损伤及其与DNA修复基因ERCC1表达变化的关系进行研究,为镉化物对机体的亚慢性损伤及其毒作用机制补充新的实验数据。
2.方法
2.1在急性毒性试验的基础上,用SPF级别SD大鼠96只按体重随机分4组,3个CdCl2染毒组(高剂量1.225mg/kg、中剂量0.612mg/kg和低剂量0.306mg/kg)和1个生理盐水对照组(0.9% NaCl),每组24只大鼠,雌雄各半,腹腔注射,每天1次,每周5天,连续14周。然后对大鼠进行24小时尿液收集,穿刺心脏采血,剖杀切取内脏器官并对其进行称重。
2.2用原子吸收分光光度法测定肝和肾组织的镉含量,计算肝脏和肾脏的脏器系数,同时从每组中随机抽出4只大鼠(雌雄各半),分别对其肝脏和肾脏进行病理切片以观察组织形态学变化。测定血清丙氨酸转氨酶(ALT)和谷草转氨酶(AST)作为肝功能生化指标,测定血中尿素氮(BUN)、血肌酐(SCR)、尿肌酐(CR)以及24小时尿蛋白(24hPro)作为肾功能生化指标。
2.3在构建亚慢性镉暴露大鼠模型的基础上,探讨DNA修复基因ERCC1在肝和肾组织中的表达情况。根据ERCC1基因的mRNA序列,用Primer Express 2.0软件设计ERCC1上下游引物。应用Trizol试剂盒并按照其一步法提取大鼠肝组织和肾组织中总RNA,经逆转录(RT)后用实时荧光定量PCR(FQ-PCR)检测方法分析其ERCC1基因的表达情况。
2.4分析雌雄大鼠的肝、肾脏器系数及其与镉含量的关系,进一步对大鼠肝脏和肾脏的ERCC1基因表达水平与肝、肾镉含量,以及肝、肾功能变化分别作关联性分析。数据均以x±s表示,运用t-检验、方差分析、Games-Howell检验、Student- Newman-Keulsa检验和相关分析等对数据进行处理,P<0.05有统计学意义。
3.结果
3.1大鼠经过不同镉浓度染毒14周后,不同镉暴露的大鼠肝、肾脏器中的镉含量均有不同程度升高,并随着镉的暴露水平的增加而升高,存在明显的剂量依赖关系(P<0.01)。实验组大鼠肝、肾组织的脏器系数均有不同程度增大,并随着镉的暴露水平的增加而增大,具有明显的剂量依赖关系(P<0.01)。实验组大鼠肝、肾组织的病理切片中与对照组相比也均观察到明显的病理学改变。提示亚慢性CdCl2染毒已经引起肝、肾靶器官不可逆的的严重损伤。
3.2亚慢性染毒试验的结果显示,CdCl2染毒的大鼠中肝功能生化指标AST和ALT的活性以及肾功能生化指标Scr、BUN和24hPro的活性等,相对于对照组均有不同程度的升高,并随着镉的暴露水平的增加而升高,具有明显的剂量-反应关系(P<0.05)。这些数据显示镉亚慢性染毒已经引起肝、肾组织的不同程度的损害并出现了功能性的改变。以上检测结果显示雌雄大鼠的变化趋势相同,而且雄性大鼠的变化有大于雌性大鼠变化的趋势。
3.3经FQ-PCR分析,肝脏和肾脏的ERCC1基因的表达量以β-actin为内参照进行标化计算,在镉高、中、低剂量染毒大鼠组中,肝脏ERCC1表达量分别是对照组的66.7%、70.9%和74.3%,而肾脏ERCC1表达量分别是对照组的69.4%、79.39%和85.2%,显示随着大鼠CdCl2暴露水平的升高而其肝、肾的ERCC1表达水平下调更明显,具有明显的剂量-反应关系(P<0.01),而且随着染镉剂量的升高雌性大鼠ERCC1表达量的降低程度比雄性大鼠更为明显。
3.4经过统计学的相关性分析,发现大鼠肝、肾靶器官的ERCC1 mRNA表达量与大鼠肝、肾中的镉蓄积浓度呈负相关关系;大鼠肝、肾中的ERCC1 mRNA表达水平还分别与肝功能生化指标(AST,ALT)和肾功能生化指标(24hpro,BUN, Scr)异常存在负相关关系,并与肝、肾组织的病理学改变相关。结果表明,肝、肾靶器官的ERCC1基因表达水平与大鼠的镉暴露程度、肝和肾组织中的镉镉蓄积浓度及其引起的内脏器官异常效应呈现出良好的负相关性(P<0.01或P<0.05)。
4.结论
4.1构建了大鼠亚慢性镉暴露模型,发现镉可以引起肝、肾脏器系数的增大和不同程度的病理改变,同时引起肝、肾生化功能的改变,有明显的剂量-反应关系,表明镉对肝、肾等靶器官均产生明显的毒性损害并得到病理学证实,为镉化物对机体的亚慢性损伤及其毒作用机制补充新的实验数据。
4.2在亚慢性镉中毒模型中观察到镉对大鼠内脏器官DNA修复基因ERCC1表达的诱导作用,揭示大鼠肝、肾ERCC1基因表达下调与肝、肾组织的镉蓄积量及其引起的内脏器官异常效应呈现出良好的剂量-反应关系,提示ERCC1基因的表达改变有可能成为一个有价值的镉亚慢性暴露或效应生物标志物。
1. Objective:
Cadmium (Cd) and its compounds are known occupational hazardous chemicals and environmental contaminants,and they can induce a wide variety of adverse health effects, even result in human tumors after absorption. According to IARC, Cd and its compounds are classified as human carcinogens, and they are the one of the most hazard metallic poisons in human. Therefor, Cd exposure and its health damage, especially toxic effects of long-term low level exposure to Cd has become a hotspot in toxicological study, in which the expression changes of DNA repair genes in rats exposed to Cd has been rarelly reported. The present objective is to investigate the the oxicity injuries and DNA repair gene ERCC1 expressions in rats exposed subchronically to Cd through establishing a model of long-term low level exposure to Cd in rats, supplement experimental data of Cd inducing subchronically damages and toxic mechanisms.
2. Methods:
2.1 Based on acute toxicity test, the 96 Sprague-Dawley rats (half male and half female) were culled by weight and randomly assigned to four experimental groups with 24 rats each group. The rats were respectively given i.p. injections of ultrapure water solution containing the CdCl2 in doses of 1.225 mg/kg,0.612 mg/kg,0.306 mg/kg body wt (5 times i.p. per week) for 14 weeks. After 14 weeks of treatment all rats were placed separately in glass metabolic cages for 24-h urine collection, as well as the blood and urine and internal organs were collected.
2.2 Cd levels were detected by atomic absorption spectrometry in liver and kidney, and their organ coefficients were respectively calculated. At the same time we select ed4 rats from every group randomly (half male and half female), and the biopsies of liver and kidney were prepared to observe the histological changes. The activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST) in serum were measured as indicators of the liver function. The blood urea nitrogen(BUN), serum creatinine(SCR), urine creatinine(CR), 24 hour protein (24hPro) were detected as parameters of the kidney function.
2.3 Through establishing a model of subchronic exposure to Cd in rats, we could explore the expressions of ERCC1 in liver and kidney. According to mRNA sequence of ERCC1, upstream and downstream primers of ERCC1 were designed by Primer Express 2.0. Using TRIzol reagent. The total RNAs from liver and kidney were isolated and the ERCC1 expressions were analysed with reverse transcrispion (RT) and fluorescent quantitative-polymerase chain reaction (FQ-PCR).
2.4 The relationships between liver, kidney coefficients and their Cd concentration, and the correlations between ERCC1 expression levels and Cd concentration in liver and kidney were analysed. Data were expressed as mean±standard deviation ( x±s), and statisticlly analysed with t-test, variance analysis, Games-Howell test, Student- Newman-Keulsa test and correlation analysis and so on. The level of significance was set at P<0.05.
3. Results:
3.1 After rats were treated by different Cd concentrations for 14 weeks, the levels of Cd concetration in liver, kidney were significantly increased compared to controls, and there were distinct dose-dependent relationships among different groups(P<0.01). The levels of organ/body coefficients in liver and kidney were significantly increased with compared to controls and there were dose-dependent relationships among different groups (P<0.01). The internal organs (liver and kidney) of rats showed pathological changes compared to control, which influenced in tissues by the administration of Cd.
3.2 As the result of subchronic experiment shown,the biochemical indicators like ALT, AST for hepatic function and 24hpro, BUN, SCR for renal function induced by Cd displayed significantly increased with the levels of Cd-exposure compared to controls, and there were dose-response relationships among different groups (P<0.05).This data indicated series of damages as well as dysfunctions had been occured in the liver, kidney by subchronic Cd-exposed. The results above were almost the same between males and females, while the viarations showed in males were more obviously than that of females.
3.3 After FQ-PCR analysis, under the inner standard ofβ-actin, showed primarily that the levels of ERCC1 expression were 66.7%、70.9%、74.3% down regulation in liver , and were 69.4%、79.39%、85.2% down regulation in the kidney of rats treated with CdCl2 in high-dose, med-dose, and low-dose, respectively (P<0.01). when compared with controls. The data above displayed a obviously dose-response relationship since the down regulations were along with Cd-exposure levels (P<0.01). Besides, the level of ERCC1 down regulation in females is a little more obviously than that in males with the Cd concentration increased (P<0.05).
3.4 The statistical correlation analysis showed that, in liver and kidney respectively, there were the negative correlation between ERCC1 under-expression and Cd cumulation. Besides in liver and kidney respectively, there were the negative correlation between ERCC1 under-expression and the biochemical indicators such as ALT, AST for hepar function and 24hpro, BUN, Scr for renal function induced, as well as the pathological changes in the liver, kidney respectively. The results showed the levels of ERCC1 factor had good negative dose-response relationship along with the Cd exposure levels in liver and kidney tissue (P<0.01or P<0.05).
4. Conclusions:
4.1 A rat model of subchronic Cd exposure was established. Cd could induce the organ coefficient of liver and kidney increasing ,various pathological changes and biochemical function changes in liver and renal, with the dose-response relationship. The results above confirm the obviously toxicity in liver and kidney induced by Cd which will provide new scientific data for long-term toxicity of Cd compounds.
4.2 Indution of DNA repair gene ERCC1 was observed in rat internal organs on the basis of the subchronic Cd-exposed model, revealing that there was a good negative dose-response relationship between the ERCC1 expression levels and Cd exposure in rats’liver and kidney, respectively. These findings indicate that expression damages of ERCC1 factor seem to be a significant biomarker of exposure or effect to Cd subchronic toxicity.
镉(Cadmium,Cd)及其化合物是常见的工业毒物和环境污物,进入机体内的镉可引起多种组织器官的损害,甚至导致肿瘤的发生。根据国际癌症研究组织(IARC)的报告,镉及其化合物是确认的第一类致癌物,是人类危害最大的金属毒物之一。因此,镉暴露及其健康损害,特别是镉低水平长期毒作用已经成为毒理学研究的热点,其中关于DNA修复基因在亚慢性镉暴露动物体内的表达变化鲜见报道。本实验通过创建大鼠亚慢性镉暴露模型,对镉低水平较长期致大鼠的损伤及其与DNA修复基因ERCC1表达变化的关系进行研究,为镉化物对机体的亚慢性损伤及其毒作用机制补充新的实验数据。
2.方法
2.1在急性毒性试验的基础上,用SPF级别SD大鼠96只按体重随机分4组,3个CdCl2染毒组(高剂量1.225mg/kg、中剂量0.612mg/kg和低剂量0.306mg/kg)和1个生理盐水对照组(0.9% NaCl),每组24只大鼠,雌雄各半,腹腔注射,每天1次,每周5天,连续14周。然后对大鼠进行24小时尿液收集,穿刺心脏采血,剖杀切取内脏器官并对其进行称重。
2.2用原子吸收分光光度法测定肝和肾组织的镉含量,计算肝脏和肾脏的脏器系数,同时从每组中随机抽出4只大鼠(雌雄各半),分别对其肝脏和肾脏进行病理切片以观察组织形态学变化。测定血清丙氨酸转氨酶(ALT)和谷草转氨酶(AST)作为肝功能生化指标,测定血中尿素氮(BUN)、血肌酐(SCR)、尿肌酐(CR)以及24小时尿蛋白(24hPro)作为肾功能生化指标。
2.3在构建亚慢性镉暴露大鼠模型的基础上,探讨DNA修复基因ERCC1在肝和肾组织中的表达情况。根据ERCC1基因的mRNA序列,用Primer Express 2.0软件设计ERCC1上下游引物。应用Trizol试剂盒并按照其一步法提取大鼠肝组织和肾组织中总RNA,经逆转录(RT)后用实时荧光定量PCR(FQ-PCR)检测方法分析其ERCC1基因的表达情况。
2.4分析雌雄大鼠的肝、肾脏器系数及其与镉含量的关系,进一步对大鼠肝脏和肾脏的ERCC1基因表达水平与肝、肾镉含量,以及肝、肾功能变化分别作关联性分析。数据均以x±s表示,运用t-检验、方差分析、Games-Howell检验、Student- Newman-Keulsa检验和相关分析等对数据进行处理,P<0.05有统计学意义。
3.结果
3.1大鼠经过不同镉浓度染毒14周后,不同镉暴露的大鼠肝、肾脏器中的镉含量均有不同程度升高,并随着镉的暴露水平的增加而升高,存在明显的剂量依赖关系(P<0.01)。实验组大鼠肝、肾组织的脏器系数均有不同程度增大,并随着镉的暴露水平的增加而增大,具有明显的剂量依赖关系(P<0.01)。实验组大鼠肝、肾组织的病理切片中与对照组相比也均观察到明显的病理学改变。提示亚慢性CdCl2染毒已经引起肝、肾靶器官不可逆的的严重损伤。
3.2亚慢性染毒试验的结果显示,CdCl2染毒的大鼠中肝功能生化指标AST和ALT的活性以及肾功能生化指标Scr、BUN和24hPro的活性等,相对于对照组均有不同程度的升高,并随着镉的暴露水平的增加而升高,具有明显的剂量-反应关系(P<0.05)。这些数据显示镉亚慢性染毒已经引起肝、肾组织的不同程度的损害并出现了功能性的改变。以上检测结果显示雌雄大鼠的变化趋势相同,而且雄性大鼠的变化有大于雌性大鼠变化的趋势。
3.3经FQ-PCR分析,肝脏和肾脏的ERCC1基因的表达量以β-actin为内参照进行标化计算,在镉高、中、低剂量染毒大鼠组中,肝脏ERCC1表达量分别是对照组的66.7%、70.9%和74.3%,而肾脏ERCC1表达量分别是对照组的69.4%、79.39%和85.2%,显示随着大鼠CdCl2暴露水平的升高而其肝、肾的ERCC1表达水平下调更明显,具有明显的剂量-反应关系(P<0.01),而且随着染镉剂量的升高雌性大鼠ERCC1表达量的降低程度比雄性大鼠更为明显。
3.4经过统计学的相关性分析,发现大鼠肝、肾靶器官的ERCC1 mRNA表达量与大鼠肝、肾中的镉蓄积浓度呈负相关关系;大鼠肝、肾中的ERCC1 mRNA表达水平还分别与肝功能生化指标(AST,ALT)和肾功能生化指标(24hpro,BUN, Scr)异常存在负相关关系,并与肝、肾组织的病理学改变相关。结果表明,肝、肾靶器官的ERCC1基因表达水平与大鼠的镉暴露程度、肝和肾组织中的镉镉蓄积浓度及其引起的内脏器官异常效应呈现出良好的负相关性(P<0.01或P<0.05)。
4.结论
4.1构建了大鼠亚慢性镉暴露模型,发现镉可以引起肝、肾脏器系数的增大和不同程度的病理改变,同时引起肝、肾生化功能的改变,有明显的剂量-反应关系,表明镉对肝、肾等靶器官均产生明显的毒性损害并得到病理学证实,为镉化物对机体的亚慢性损伤及其毒作用机制补充新的实验数据。
4.2在亚慢性镉中毒模型中观察到镉对大鼠内脏器官DNA修复基因ERCC1表达的诱导作用,揭示大鼠肝、肾ERCC1基因表达下调与肝、肾组织的镉蓄积量及其引起的内脏器官异常效应呈现出良好的剂量-反应关系,提示ERCC1基因的表达改变有可能成为一个有价值的镉亚慢性暴露或效应生物标志物。
1. Objective:
Cadmium (Cd) and its compounds are known occupational hazardous chemicals and environmental contaminants,and they can induce a wide variety of adverse health effects, even result in human tumors after absorption. According to IARC, Cd and its compounds are classified as human carcinogens, and they are the one of the most hazard metallic poisons in human. Therefor, Cd exposure and its health damage, especially toxic effects of long-term low level exposure to Cd has become a hotspot in toxicological study, in which the expression changes of DNA repair genes in rats exposed to Cd has been rarelly reported. The present objective is to investigate the the oxicity injuries and DNA repair gene ERCC1 expressions in rats exposed subchronically to Cd through establishing a model of long-term low level exposure to Cd in rats, supplement experimental data of Cd inducing subchronically damages and toxic mechanisms.
2. Methods:
2.1 Based on acute toxicity test, the 96 Sprague-Dawley rats (half male and half female) were culled by weight and randomly assigned to four experimental groups with 24 rats each group. The rats were respectively given i.p. injections of ultrapure water solution containing the CdCl2 in doses of 1.225 mg/kg,0.612 mg/kg,0.306 mg/kg body wt (5 times i.p. per week) for 14 weeks. After 14 weeks of treatment all rats were placed separately in glass metabolic cages for 24-h urine collection, as well as the blood and urine and internal organs were collected.
2.2 Cd levels were detected by atomic absorption spectrometry in liver and kidney, and their organ coefficients were respectively calculated. At the same time we select ed4 rats from every group randomly (half male and half female), and the biopsies of liver and kidney were prepared to observe the histological changes. The activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST) in serum were measured as indicators of the liver function. The blood urea nitrogen(BUN), serum creatinine(SCR), urine creatinine(CR), 24 hour protein (24hPro) were detected as parameters of the kidney function.
2.3 Through establishing a model of subchronic exposure to Cd in rats, we could explore the expressions of ERCC1 in liver and kidney. According to mRNA sequence of ERCC1, upstream and downstream primers of ERCC1 were designed by Primer Express 2.0. Using TRIzol reagent. The total RNAs from liver and kidney were isolated and the ERCC1 expressions were analysed with reverse transcrispion (RT) and fluorescent quantitative-polymerase chain reaction (FQ-PCR).
2.4 The relationships between liver, kidney coefficients and their Cd concentration, and the correlations between ERCC1 expression levels and Cd concentration in liver and kidney were analysed. Data were expressed as mean±standard deviation ( x±s), and statisticlly analysed with t-test, variance analysis, Games-Howell test, Student- Newman-Keulsa test and correlation analysis and so on. The level of significance was set at P<0.05.
3. Results:
3.1 After rats were treated by different Cd concentrations for 14 weeks, the levels of Cd concetration in liver, kidney were significantly increased compared to controls, and there were distinct dose-dependent relationships among different groups(P<0.01). The levels of organ/body coefficients in liver and kidney were significantly increased with compared to controls and there were dose-dependent relationships among different groups (P<0.01). The internal organs (liver and kidney) of rats showed pathological changes compared to control, which influenced in tissues by the administration of Cd.
3.2 As the result of subchronic experiment shown,the biochemical indicators like ALT, AST for hepatic function and 24hpro, BUN, SCR for renal function induced by Cd displayed significantly increased with the levels of Cd-exposure compared to controls, and there were dose-response relationships among different groups (P<0.05).This data indicated series of damages as well as dysfunctions had been occured in the liver, kidney by subchronic Cd-exposed. The results above were almost the same between males and females, while the viarations showed in males were more obviously than that of females.
3.3 After FQ-PCR analysis, under the inner standard ofβ-actin, showed primarily that the levels of ERCC1 expression were 66.7%、70.9%、74.3% down regulation in liver , and were 69.4%、79.39%、85.2% down regulation in the kidney of rats treated with CdCl2 in high-dose, med-dose, and low-dose, respectively (P<0.01). when compared with controls. The data above displayed a obviously dose-response relationship since the down regulations were along with Cd-exposure levels (P<0.01). Besides, the level of ERCC1 down regulation in females is a little more obviously than that in males with the Cd concentration increased (P<0.05).
3.4 The statistical correlation analysis showed that, in liver and kidney respectively, there were the negative correlation between ERCC1 under-expression and Cd cumulation. Besides in liver and kidney respectively, there were the negative correlation between ERCC1 under-expression and the biochemical indicators such as ALT, AST for hepar function and 24hpro, BUN, Scr for renal function induced, as well as the pathological changes in the liver, kidney respectively. The results showed the levels of ERCC1 factor had good negative dose-response relationship along with the Cd exposure levels in liver and kidney tissue (P<0.01or P<0.05).
4. Conclusions:
4.1 A rat model of subchronic Cd exposure was established. Cd could induce the organ coefficient of liver and kidney increasing ,various pathological changes and biochemical function changes in liver and renal, with the dose-response relationship. The results above confirm the obviously toxicity in liver and kidney induced by Cd which will provide new scientific data for long-term toxicity of Cd compounds.
4.2 Indution of DNA repair gene ERCC1 was observed in rat internal organs on the basis of the subchronic Cd-exposed model, revealing that there was a good negative dose-response relationship between the ERCC1 expression levels and Cd exposure in rats’liver and kidney, respectively. These findings indicate that expression damages of ERCC1 factor seem to be a significant biomarker of exposure or effect to Cd subchronic toxicity.
引文
1. Diao WP, Ni WZ, Ma HY, Yang XE. Cadmium pollution in paddy soil as affected by different rice(Oryza sativa L.) cultivars. Bull Environ Contam Toxicol,2005,75(4): 731-738.
2. Sorahan T, Esmen NA. Lung cancer mortality in UK nickel-cadmium battery workers, 1947-2000. Occup Environ Med 2004: 61(2), 108-116.
3. Koyu A, Gokcimen A, Ozguner F, Bayram DS, Kocak A.. Evaluation of the effects of cadmium on rat liver. Mol Cell Biochem,2006,20: 1-5.
4.陶炼挥,王翔朴.镉中毒肾损害大鼠尿中不同分子量镉、锌结合物的研究.卫生毒理学杂志,1990,4(4):210-2.
5. Massadeh AM, Al-Safi SA, Momani IF, et al. Garlic (allium sativum L) as a potential antidote for cadmium and Lead intoxication: cadmium and lead distribution and analysis in different mice organs[J]. Biological Trace Element Research, 2007, 120(1-3): 227-234.
6. Manca D,Ricard AC,Trottier B,et a1.Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride[J].Toxicology,1991,67(3):303-323.
7. Kartelan. Cadmiuminduead decrenent of the LH Ieeeptor expression and cAMP levels in the testis of rats [J].Toxicology,2003,183:57-63.
8. Kriegel AM, Soliman AS, Zhang Q, El-Ghawalby N, Ezzat F, Soultan A, Abdel-Wahab M, Fathy O, Ebidi G, Bassiouni N, Hamilton SR, Abbruzzese JL, Lacey MR, Blake DA. Serum cadmium levels in pancreatic cancer patients from the East Nile Delta region of Egypt. Environ Health Perspect 2006, 114(1): 113-119.
9. Sorahan T. Mortality from lung cancer among a cohort of nickel cadmium battery workers: 1946-84. Br J Ind Med 1987, 44: 803-809.
10. Goyer RA, Liu J, Waalkes MP. Cadmium and cancer of prostate and testis. Biometals 2004, 17(5): 555-558.
11. Fay RM, Mumtaz MM. Development of a priority list of chemical mixture occurring at 1188 hazardous waste sites, using the HazDat database. Food Chem Toxicol. 1996; 34:1163-1165.
12. IARC. Beryllium, cadmium, mercury and exposures in the glass manufacturing industry, Lyon, France. International Agency for Research on Cancer 1993; Vol.58: 119-238.
13. Barja,G.,Mitochondrial flee radical production and aging in mammals and birds Ann N YAcadSei,1998.854:P.224-38.
14. Mandavilli,B.S.,J.H.Santos,and B.Van Houten,Mitochondrial DNA repair and aging.Mutat Res,2002.509(1-2):P.127-51.
15. Bouziane,M.,F Miao,N.Ye,G.Holmquist,G.Chyzak,and tR.0’Connor,Repair ofDNA alkylation damage.Acta Biochim Pol,1998.45(1):P.191-202.
16. Hill,M.A.,Radiation damage to DNA:the importance of track structure,Radiat Meas,1999,31(1-6):P.15-23.
17. Cohen , S . M . and S . J . Lippard , Cisplatin : from DNA damage to cancer chemotherapy.ProgNucleicAcidResMotBlot,2001.67:P.93-130.
18. Aboussekhra,A.,M,Biggerstaff,M.K.Shivji,J.A.Vilpo,V Moncollin,MN.Podnst,M.Protic,U,Hubscher,J.M.Egly,and R.D.Wood,Mammalian DNA nucleotide excision repair reconstituted with purified protein components Cell 1995,80(6):P.859-68.
19. Mn,D.,M.Wakasugi,D.S Hsu,and A,Sancar,Characterization of reaction intermediates of human excision repair nuclease J Biol Chem,1997.272(46):P.28971-9.
20. Reardon.J.T and A.Sancar,Molecular anatomy of the human excision nucIease assembled at sites of DNA damage.Idol Cell Biol,2002.22(16):P.5938-45.
21. Matsunaga,T,D.Mu,C.H.Park,J,T.Reardon,and A.Sancar,Human DNA repair excision nuclease.Analysis of the roles of the summits involved in dual incisions by using anti-XPG and anti.ERCCl antibodies.J Biol Chem,1995.270(35):P.20862-9.
22. Kuraoka。I W.R.Kobertz,R.R.Ariza,M.Biggerstaff,J.M.Essigmann,and R.D.Wood,Repair ofan interstrand DNA cross-link initiated by ERCCl-XPF repair recombination nuclease.JBiol Chem,2000.275(34):P.26632-6.
23. Araujo,S.J.,F.Tirode,F,Coin,H.Pospiech,J.E.Syvaoja,M.Stucki,U.Hubscher,J.M.Egly,and R.D.Wood,Nucleotide excision repair of DNA with recombinant human proteins:definition of the minimal set of factors.Active forms of TFIIH,and modulation by CAK.Genes Dev,2000.14(3):P.349-59.
24. Hsia,K.T,M.R.Millar,S.King,J.Selfridge,N.J.Redhead,D.W Melton andPT Saunders.DNA repair gene Erccl is essential for normal spermatogenesis and oogenesis and for fimctional integrity of germ cell DNA in the mouse Development,2003.130(2):P.369-378.
25. Chipchase,M.D.and D.W Melton,The formation of UV.Induced chromosome aberrations Involves ERCCl and XPF but not other nucleotideexcision repair genes.DNA Repair搿msO,2002.1(4):P.335-40.
26. Gelmini S, Orlando C, Sestini R, Vona G, Pinzani P, Ruocco L, Pazzagli M. Quantitative polymerase chain reaction-based homogeneous assay with fluorogenic probes to measure c-erbB-2 oncogene amplification. Clin. Chem. 1997,43(5): 752-758.
27. KennethJ.Livak,ThomasD.Schmittgen. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 22DDCT Method. METHODS,25: 402–408(2001).
28.张驰宇,徐顺高,黄新祥一种新颖简便的荧光实时RT-PCR相对定量方法的建立。Prog. Biochem. Biophys. 2005:32(9).
29.蔡燕侠.醋酸铅染毒大鼠肾脏毒性作用研究Rl.山西医科大学硕士毕业论文,2005.
30. KlaassenC.D.ed.Casarett and Doull’s Toxicology(sixth edition). McGraw-Hill,2002.
31. Bernard A,Lauwerys R.Handbook of Experimental Pharmacology [J].Berlin:Springer-Verlag,1986,80(1):141-150.
32.刘毓谷.卫生毒理学基础[M].第2版.北京:人民卫生出版社, 1999.
33.黄雅卿,张文昌,李煌元.镉对雌性大鼠体重变化和卵巢脏器系数的影响[J].职业与健康, 2003,19(7):7-9.
34.顾刘金,杨校华,陈琼姜,孙建析等.SD大鼠脏器重量及脏器系数正常参考值研究.环境与职业医学,2005, 22(5):453-454.
35.江泉观主编:基础毒理学,北京医学院出版社,1985.
36.沈建忠.物毒理学[M].北京:中国农业出版社,2002.
37. Elez D, Dundjerski J, Matic G Cadmium affects the redox state of rat liver glucocorticoid receptor[J]. Cell Biol Toxicol, 2001, 17(3):169-177.
38.陈龙,任文华,朱善良,高伟,周娟,蒋英子,谷宇.慢性镉负荷雄性大鼠的睾丸及生殖内分泌功能活动[J].生理学报,2002,54(3):258-262.
39. Yang XF, Wang SY, Zhao RC, Ao SQ, Xu LC, Wang XR. Changes in tissue metals aftercadmium intoxication and intervention with chlorpro- mazine in male rats[J]. Biomed Environ Sci, 2000,13(1): 19-25.
40. Yu RA, Chen X, Lu W. Study on cadmium-induced hepatocellular apoptosis in rats[J]. Wei Sheng Yan Jiu, 2001,30(5): 271-272.
41. Zirogiannis KN, Panoutsopoulos GI, Demonakou MD, Hereti RI, Alexandropoulou KN, Mykoniatis MG.Effect of hepatic stimulator substance (HSS) on cadmium-induced acute hepatotoxicity in the rat liver[J]. Dig Dis Sci,2004,49(6): 1019-1028.
42.王捍东,邢华,卞建春,等.镉对原代培养大鼠肝细胞的损伤作用[J].中国兽医学报,2000,20(6):580-583.
43.成峰,陈学敏,王桂珍.硒对镉在大鼠肝脏亚细胞分布及脂质过氧化作用的影响[J].卫生研究,1996,25(1):32-34.
44.秀凤,唐玲芳.镉的致癌性研究进展[J].职业医学,1998,25(2):46-49.
45. Shibasaki T, Nakano H, Ohno I, et a1.Effect of polyaspartic acid on CdCl2 - induced nephrotoxicity in the rat.Biol Trace Elem Res,1993,37:261 - 267.
46.逄兵,金泰磷,胡云平,等.重复注射镉金属硫蛋白诱导小鼠肾脏金属硫蛋白基因的表达.中华劳动卫生职业病杂志,2001,19(40):42.
47. Tanimoto A,Hamada T,Koide 0. Cell death and regeneration of renal proximal tubular cells,in rats with subchronic cadmium intoxi- cation.[J]Toxicol Pathol,1993,21(4):341-352.
48. Patrick L. Toxic metals and antioxidants[J].Altern Med Rev,2003,8: 106-128.
49. Nordberg GF. In“cadmium in the Human Enviroment,Toxicity and Car-cinogencity". [M]Lyon,IARC,1992:3.
50. Tanimoto A, Hamada T,Higashi K, et a1.Distribution of cadmium and metallo- thionein in CdCI2 -exposed rat kidney:relationship wi t h apoptosis and regenera- tion. Pathol Int,1999,49:125-132.
51.孙帅.血清酶AST/ALT比值在肝病中的意义.中华医药杂志,2005,10:5 (10).
52.杜理国,王翔朴,高泽宜.镉在肾皮质及亚细胞器中的分布与肾损害的关系.中华预防医学杂志,1998:32(5).
53.李克玲,王谦,耿益民,等.肾炎益气液对大鼠肾毒血清性肾炎肾功能、肾组织病理学的影响[ J ].中国病理生理杂志, 2004, 20 (2) : 200-203.
54.孟小芹,丁国华.蛋白尿的非特异性治疗[ J ].临床肾脏病杂志, 2005, 5 (2) : 93- 5.
55.孙世澜,周朝阳主编.肾病理论与实践[M].北京:人民军医出版社,2005:5-10.
56. Jafar TH, Stark PC, SchmidCH. Proteinuria as amodifiable risk factor for the progression of non - diabetic renal diseases[ J ]. Kidney Int, 2001, 60: 1131 - 1140.
57. Van Duin M, de Wit J, Odijk H, et al. Molecular characterization of the human excision repair gene ERCC-1:cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10. Cell, 1986,44(6):913-923.
58. Lehmann AR. Workshop on Eukaryotic DNA repair genes and gene products. Cancer Res, 1995, 55:968-970.
59. Vogelstein B, Kinzler RW. The mulistep nature of cancer. Trends Cgenet,1993,9: 138 -141.
60. Fatur T, Lab TT, Filipic M. Cadmium inhibits of UV-,methylmethane- sulfonate and N-muthyl-N-nitrosourea-induced DNA damage in Chinese hamster ovary cells.Mutat Ras,2003,529:109-116.
61. Hartwig A. Carcinogenicity of metal compounds: possible role of DNA repair inhibition. Toxicol Lett, 1998, 28: 235-239.
62.周志衡,雷毅雄,王彩霞,王敏,魏莲,纪卫东.镉恶化转化16HBE细胞中核苷酸切除修复基因的表达.毒理学杂志,2008,8:22(4).
63.刘毓谷.卫生毒理学基础[M ].第2版.北京:人民卫生出版社, 1999.
1. Boguszewska A, Pasternak K. Cadmium--influence on biochemical processes of the human organism. Ann Univ Mariae Curie Sklodowska 2004; 59(2): 519-523.
2. Wennberg M, Lundh T, Bergdahl IA, Hallmans G, Jansson JH, Stegmayr B, Custodio HM, Skerfving S. Time trends in burdens of cadmium, lead, and mercury in the population of northern Sweden. Environ Res 2006; 100(3):
330-338.
3. Nordberg G, ChinaCad Group. Cadmium and human health: A perspective based on recent studies in China. J Trace Elem Exp Med 2003; 16: 307-319.
4. Kriegel AM, Soliman AS, Zhang Q, El-Ghawalby N, Ezzat F, Soultan A, Abdel-Wahab M, Fathy O, Ebidi G, Bassiouni N, Hamilton SR, Abbruzzese JL, Lacey MR, Blake DA. Serum cadmium levels in pancreatic cancer patients from the East Nile Delta region of Egypt. Environ Health Perspect 2006; 114(1): 13-119.
5. Sorahan T. Mortality from lung cancer among a cohort of nickel cadmium battery workers: 1946-84. Br J Ind Med 1987; 44: 803-809.
6. Goyer RA, Liu J, Waalkes MP. Cadmium and cancer of prostate and testis. Biometals, 2004, 17(5): 555-558.
7.蒋英子,陈龙,高伟等.镉暴露大鼠血中白细胞介素-2和皮质醇水平及白细胞免疫功能的变化.环境与健康杂志, 2002,19(5):364-366.
8.陈敏,谢吉民,程晓农等.镉对小鼠肝脏的毒性作用机理探讨.江苏大学学报, (医学版). 2002,12(4):321-323.
9. IARC.Beryllium,cadmium,mercury and exposures in the glass manufacturing industry, Lyon, France. International Agency for Research on Cancer, 1993, Vol.58: 119-238.
10. Mouron SA, Grillo CA , Dulout FN, etal. A comparative investigation ofDNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells [J].Mutat-Res,2004,568(2):221-31.
11.余日安,陈学敏,鲁文清.镉对大鼠肝脏细胞凋亡的影响.卫生研究, 2001,30(5):271-272.
12. Han C,eta1.Inhibition by germanium oxide of the mutagenlcity of cadmium chloride in various genotoximty assays . Food Chem Toxicol,1992,30(6):521 .
13. Terracio, L,et a1.Oncogenlcity of rat prostate cells transformed in vitro with cadmium chloride.Arch Toxicol,1988,61:450.
14. Ord MJ,et a1.Changes in muntjac fibroblasts associated with the acquisition of cadmium resistance.Areh Toxi col. 1990, 64(2):77.
15.俞萍,唐玲芳.镉致癌机理研究进展[J] .国外医学卫生学分册,1998,25(4):206-217.
16. Qchi T,et a1.Indirect evidsnve for the induction of aprooxidant stats by cadmium chlorid in cultured mammalian cells and a possible mechanism for the induction.Mut Res,1983,180:257.
17. Wood RD, Mitchell M, Sgouros J, et al. Haman DNA Repair Genes. Sicence, 2001,291(5507):1284-1294.
18. YuZ, ChenJ, Ford BN, etal. Human DNA repair systems: an overview. Environ MolMut, 1999, 33:3-20.
19.周志衡,雷毅雄,王彩霞,王敏,魏莲,纪卫东.镉恶化转化16HBE细胞中核苷酸切除修复基因的表达[J]. Toxicol August, 2008, 22(4):255.
20.周志衡,雷毅雄,王彩霞,王敏,魏莲,纪卫东.配修复基因在氯化镉致16HBE细胞转化中作用.Chin J Public HealthJul, 2008,24 (7):789.
21. Liu L,Qin X,Gerson SL. Eeduced lung tumorigenesis in human methylguagene within the target cell[J]. Careinogenesis,1999,20(2):279-284.
22.宁瑞玲,宋向群,罗园,等. ERCC1、MT、P53和Bcl-2表达与含铂方案治疗晚期NSCLC的关系研究[J].中国肺癌杂志,2006,9(4):373-375.
23. Zhou W,Liu G,Park S,et al. Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer[J]. Cancer Epidermal Biomarkers Prev,2005,1(2):491-496.
24.吕嘉春,吴中亮,施侣元,等.核苷酸切除修复基因表达低下与肺癌的关系[J].中国公共卫生,2003,19(7):780-782.
25. Shirota,Y,Stoehlmacher,J.,Brabender,J,,Xiong,YP,Uetake,H.,Danenberg,K.D.,Groshen,S.,Tsao-Wei,D.D.,Danenberg,EV.,and Lenz,H.J.,ERCC 1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy.JCiin Oncol,2001.19(23):P.4298—304.
2. Sorahan T, Esmen NA. Lung cancer mortality in UK nickel-cadmium battery workers, 1947-2000. Occup Environ Med 2004: 61(2), 108-116.
3. Koyu A, Gokcimen A, Ozguner F, Bayram DS, Kocak A.. Evaluation of the effects of cadmium on rat liver. Mol Cell Biochem,2006,20: 1-5.
4.陶炼挥,王翔朴.镉中毒肾损害大鼠尿中不同分子量镉、锌结合物的研究.卫生毒理学杂志,1990,4(4):210-2.
5. Massadeh AM, Al-Safi SA, Momani IF, et al. Garlic (allium sativum L) as a potential antidote for cadmium and Lead intoxication: cadmium and lead distribution and analysis in different mice organs[J]. Biological Trace Element Research, 2007, 120(1-3): 227-234.
6. Manca D,Ricard AC,Trottier B,et a1.Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride[J].Toxicology,1991,67(3):303-323.
7. Kartelan. Cadmiuminduead decrenent of the LH Ieeeptor expression and cAMP levels in the testis of rats [J].Toxicology,2003,183:57-63.
8. Kriegel AM, Soliman AS, Zhang Q, El-Ghawalby N, Ezzat F, Soultan A, Abdel-Wahab M, Fathy O, Ebidi G, Bassiouni N, Hamilton SR, Abbruzzese JL, Lacey MR, Blake DA. Serum cadmium levels in pancreatic cancer patients from the East Nile Delta region of Egypt. Environ Health Perspect 2006, 114(1): 113-119.
9. Sorahan T. Mortality from lung cancer among a cohort of nickel cadmium battery workers: 1946-84. Br J Ind Med 1987, 44: 803-809.
10. Goyer RA, Liu J, Waalkes MP. Cadmium and cancer of prostate and testis. Biometals 2004, 17(5): 555-558.
11. Fay RM, Mumtaz MM. Development of a priority list of chemical mixture occurring at 1188 hazardous waste sites, using the HazDat database. Food Chem Toxicol. 1996; 34:1163-1165.
12. IARC. Beryllium, cadmium, mercury and exposures in the glass manufacturing industry, Lyon, France. International Agency for Research on Cancer 1993; Vol.58: 119-238.
13. Barja,G.,Mitochondrial flee radical production and aging in mammals and birds Ann N YAcadSei,1998.854:P.224-38.
14. Mandavilli,B.S.,J.H.Santos,and B.Van Houten,Mitochondrial DNA repair and aging.Mutat Res,2002.509(1-2):P.127-51.
15. Bouziane,M.,F Miao,N.Ye,G.Holmquist,G.Chyzak,and tR.0’Connor,Repair ofDNA alkylation damage.Acta Biochim Pol,1998.45(1):P.191-202.
16. Hill,M.A.,Radiation damage to DNA:the importance of track structure,Radiat Meas,1999,31(1-6):P.15-23.
17. Cohen , S . M . and S . J . Lippard , Cisplatin : from DNA damage to cancer chemotherapy.ProgNucleicAcidResMotBlot,2001.67:P.93-130.
18. Aboussekhra,A.,M,Biggerstaff,M.K.Shivji,J.A.Vilpo,V Moncollin,MN.Podnst,M.Protic,U,Hubscher,J.M.Egly,and R.D.Wood,Mammalian DNA nucleotide excision repair reconstituted with purified protein components Cell 1995,80(6):P.859-68.
19. Mn,D.,M.Wakasugi,D.S Hsu,and A,Sancar,Characterization of reaction intermediates of human excision repair nuclease J Biol Chem,1997.272(46):P.28971-9.
20. Reardon.J.T and A.Sancar,Molecular anatomy of the human excision nucIease assembled at sites of DNA damage.Idol Cell Biol,2002.22(16):P.5938-45.
21. Matsunaga,T,D.Mu,C.H.Park,J,T.Reardon,and A.Sancar,Human DNA repair excision nuclease.Analysis of the roles of the summits involved in dual incisions by using anti-XPG and anti.ERCCl antibodies.J Biol Chem,1995.270(35):P.20862-9.
22. Kuraoka。I W.R.Kobertz,R.R.Ariza,M.Biggerstaff,J.M.Essigmann,and R.D.Wood,Repair ofan interstrand DNA cross-link initiated by ERCCl-XPF repair recombination nuclease.JBiol Chem,2000.275(34):P.26632-6.
23. Araujo,S.J.,F.Tirode,F,Coin,H.Pospiech,J.E.Syvaoja,M.Stucki,U.Hubscher,J.M.Egly,and R.D.Wood,Nucleotide excision repair of DNA with recombinant human proteins:definition of the minimal set of factors.Active forms of TFIIH,and modulation by CAK.Genes Dev,2000.14(3):P.349-59.
24. Hsia,K.T,M.R.Millar,S.King,J.Selfridge,N.J.Redhead,D.W Melton andPT Saunders.DNA repair gene Erccl is essential for normal spermatogenesis and oogenesis and for fimctional integrity of germ cell DNA in the mouse Development,2003.130(2):P.369-378.
25. Chipchase,M.D.and D.W Melton,The formation of UV.Induced chromosome aberrations Involves ERCCl and XPF but not other nucleotideexcision repair genes.DNA Repair搿msO,2002.1(4):P.335-40.
26. Gelmini S, Orlando C, Sestini R, Vona G, Pinzani P, Ruocco L, Pazzagli M. Quantitative polymerase chain reaction-based homogeneous assay with fluorogenic probes to measure c-erbB-2 oncogene amplification. Clin. Chem. 1997,43(5): 752-758.
27. KennethJ.Livak,ThomasD.Schmittgen. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 22DDCT Method. METHODS,25: 402–408(2001).
28.张驰宇,徐顺高,黄新祥一种新颖简便的荧光实时RT-PCR相对定量方法的建立。Prog. Biochem. Biophys. 2005:32(9).
29.蔡燕侠.醋酸铅染毒大鼠肾脏毒性作用研究Rl.山西医科大学硕士毕业论文,2005.
30. KlaassenC.D.ed.Casarett and Doull’s Toxicology(sixth edition). McGraw-Hill,2002.
31. Bernard A,Lauwerys R.Handbook of Experimental Pharmacology [J].Berlin:Springer-Verlag,1986,80(1):141-150.
32.刘毓谷.卫生毒理学基础[M].第2版.北京:人民卫生出版社, 1999.
33.黄雅卿,张文昌,李煌元.镉对雌性大鼠体重变化和卵巢脏器系数的影响[J].职业与健康, 2003,19(7):7-9.
34.顾刘金,杨校华,陈琼姜,孙建析等.SD大鼠脏器重量及脏器系数正常参考值研究.环境与职业医学,2005, 22(5):453-454.
35.江泉观主编:基础毒理学,北京医学院出版社,1985.
36.沈建忠.物毒理学[M].北京:中国农业出版社,2002.
37. Elez D, Dundjerski J, Matic G Cadmium affects the redox state of rat liver glucocorticoid receptor[J]. Cell Biol Toxicol, 2001, 17(3):169-177.
38.陈龙,任文华,朱善良,高伟,周娟,蒋英子,谷宇.慢性镉负荷雄性大鼠的睾丸及生殖内分泌功能活动[J].生理学报,2002,54(3):258-262.
39. Yang XF, Wang SY, Zhao RC, Ao SQ, Xu LC, Wang XR. Changes in tissue metals aftercadmium intoxication and intervention with chlorpro- mazine in male rats[J]. Biomed Environ Sci, 2000,13(1): 19-25.
40. Yu RA, Chen X, Lu W. Study on cadmium-induced hepatocellular apoptosis in rats[J]. Wei Sheng Yan Jiu, 2001,30(5): 271-272.
41. Zirogiannis KN, Panoutsopoulos GI, Demonakou MD, Hereti RI, Alexandropoulou KN, Mykoniatis MG.Effect of hepatic stimulator substance (HSS) on cadmium-induced acute hepatotoxicity in the rat liver[J]. Dig Dis Sci,2004,49(6): 1019-1028.
42.王捍东,邢华,卞建春,等.镉对原代培养大鼠肝细胞的损伤作用[J].中国兽医学报,2000,20(6):580-583.
43.成峰,陈学敏,王桂珍.硒对镉在大鼠肝脏亚细胞分布及脂质过氧化作用的影响[J].卫生研究,1996,25(1):32-34.
44.秀凤,唐玲芳.镉的致癌性研究进展[J].职业医学,1998,25(2):46-49.
45. Shibasaki T, Nakano H, Ohno I, et a1.Effect of polyaspartic acid on CdCl2 - induced nephrotoxicity in the rat.Biol Trace Elem Res,1993,37:261 - 267.
46.逄兵,金泰磷,胡云平,等.重复注射镉金属硫蛋白诱导小鼠肾脏金属硫蛋白基因的表达.中华劳动卫生职业病杂志,2001,19(40):42.
47. Tanimoto A,Hamada T,Koide 0. Cell death and regeneration of renal proximal tubular cells,in rats with subchronic cadmium intoxi- cation.[J]Toxicol Pathol,1993,21(4):341-352.
48. Patrick L. Toxic metals and antioxidants[J].Altern Med Rev,2003,8: 106-128.
49. Nordberg GF. In“cadmium in the Human Enviroment,Toxicity and Car-cinogencity". [M]Lyon,IARC,1992:3.
50. Tanimoto A, Hamada T,Higashi K, et a1.Distribution of cadmium and metallo- thionein in CdCI2 -exposed rat kidney:relationship wi t h apoptosis and regenera- tion. Pathol Int,1999,49:125-132.
51.孙帅.血清酶AST/ALT比值在肝病中的意义.中华医药杂志,2005,10:5 (10).
52.杜理国,王翔朴,高泽宜.镉在肾皮质及亚细胞器中的分布与肾损害的关系.中华预防医学杂志,1998:32(5).
53.李克玲,王谦,耿益民,等.肾炎益气液对大鼠肾毒血清性肾炎肾功能、肾组织病理学的影响[ J ].中国病理生理杂志, 2004, 20 (2) : 200-203.
54.孟小芹,丁国华.蛋白尿的非特异性治疗[ J ].临床肾脏病杂志, 2005, 5 (2) : 93- 5.
55.孙世澜,周朝阳主编.肾病理论与实践[M].北京:人民军医出版社,2005:5-10.
56. Jafar TH, Stark PC, SchmidCH. Proteinuria as amodifiable risk factor for the progression of non - diabetic renal diseases[ J ]. Kidney Int, 2001, 60: 1131 - 1140.
57. Van Duin M, de Wit J, Odijk H, et al. Molecular characterization of the human excision repair gene ERCC-1:cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10. Cell, 1986,44(6):913-923.
58. Lehmann AR. Workshop on Eukaryotic DNA repair genes and gene products. Cancer Res, 1995, 55:968-970.
59. Vogelstein B, Kinzler RW. The mulistep nature of cancer. Trends Cgenet,1993,9: 138 -141.
60. Fatur T, Lab TT, Filipic M. Cadmium inhibits of UV-,methylmethane- sulfonate and N-muthyl-N-nitrosourea-induced DNA damage in Chinese hamster ovary cells.Mutat Ras,2003,529:109-116.
61. Hartwig A. Carcinogenicity of metal compounds: possible role of DNA repair inhibition. Toxicol Lett, 1998, 28: 235-239.
62.周志衡,雷毅雄,王彩霞,王敏,魏莲,纪卫东.镉恶化转化16HBE细胞中核苷酸切除修复基因的表达.毒理学杂志,2008,8:22(4).
63.刘毓谷.卫生毒理学基础[M ].第2版.北京:人民卫生出版社, 1999.
1. Boguszewska A, Pasternak K. Cadmium--influence on biochemical processes of the human organism. Ann Univ Mariae Curie Sklodowska 2004; 59(2): 519-523.
2. Wennberg M, Lundh T, Bergdahl IA, Hallmans G, Jansson JH, Stegmayr B, Custodio HM, Skerfving S. Time trends in burdens of cadmium, lead, and mercury in the population of northern Sweden. Environ Res 2006; 100(3):
330-338.
3. Nordberg G, ChinaCad Group. Cadmium and human health: A perspective based on recent studies in China. J Trace Elem Exp Med 2003; 16: 307-319.
4. Kriegel AM, Soliman AS, Zhang Q, El-Ghawalby N, Ezzat F, Soultan A, Abdel-Wahab M, Fathy O, Ebidi G, Bassiouni N, Hamilton SR, Abbruzzese JL, Lacey MR, Blake DA. Serum cadmium levels in pancreatic cancer patients from the East Nile Delta region of Egypt. Environ Health Perspect 2006; 114(1): 13-119.
5. Sorahan T. Mortality from lung cancer among a cohort of nickel cadmium battery workers: 1946-84. Br J Ind Med 1987; 44: 803-809.
6. Goyer RA, Liu J, Waalkes MP. Cadmium and cancer of prostate and testis. Biometals, 2004, 17(5): 555-558.
7.蒋英子,陈龙,高伟等.镉暴露大鼠血中白细胞介素-2和皮质醇水平及白细胞免疫功能的变化.环境与健康杂志, 2002,19(5):364-366.
8.陈敏,谢吉民,程晓农等.镉对小鼠肝脏的毒性作用机理探讨.江苏大学学报, (医学版). 2002,12(4):321-323.
9. IARC.Beryllium,cadmium,mercury and exposures in the glass manufacturing industry, Lyon, France. International Agency for Research on Cancer, 1993, Vol.58: 119-238.
10. Mouron SA, Grillo CA , Dulout FN, etal. A comparative investigation ofDNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells [J].Mutat-Res,2004,568(2):221-31.
11.余日安,陈学敏,鲁文清.镉对大鼠肝脏细胞凋亡的影响.卫生研究, 2001,30(5):271-272.
12. Han C,eta1.Inhibition by germanium oxide of the mutagenlcity of cadmium chloride in various genotoximty assays . Food Chem Toxicol,1992,30(6):521 .
13. Terracio, L,et a1.Oncogenlcity of rat prostate cells transformed in vitro with cadmium chloride.Arch Toxicol,1988,61:450.
14. Ord MJ,et a1.Changes in muntjac fibroblasts associated with the acquisition of cadmium resistance.Areh Toxi col. 1990, 64(2):77.
15.俞萍,唐玲芳.镉致癌机理研究进展[J] .国外医学卫生学分册,1998,25(4):206-217.
16. Qchi T,et a1.Indirect evidsnve for the induction of aprooxidant stats by cadmium chlorid in cultured mammalian cells and a possible mechanism for the induction.Mut Res,1983,180:257.
17. Wood RD, Mitchell M, Sgouros J, et al. Haman DNA Repair Genes. Sicence, 2001,291(5507):1284-1294.
18. YuZ, ChenJ, Ford BN, etal. Human DNA repair systems: an overview. Environ MolMut, 1999, 33:3-20.
19.周志衡,雷毅雄,王彩霞,王敏,魏莲,纪卫东.镉恶化转化16HBE细胞中核苷酸切除修复基因的表达[J]. Toxicol August, 2008, 22(4):255.
20.周志衡,雷毅雄,王彩霞,王敏,魏莲,纪卫东.配修复基因在氯化镉致16HBE细胞转化中作用.Chin J Public HealthJul, 2008,24 (7):789.
21. Liu L,Qin X,Gerson SL. Eeduced lung tumorigenesis in human methylguagene within the target cell[J]. Careinogenesis,1999,20(2):279-284.
22.宁瑞玲,宋向群,罗园,等. ERCC1、MT、P53和Bcl-2表达与含铂方案治疗晚期NSCLC的关系研究[J].中国肺癌杂志,2006,9(4):373-375.
23. Zhou W,Liu G,Park S,et al. Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer[J]. Cancer Epidermal Biomarkers Prev,2005,1(2):491-496.
24.吕嘉春,吴中亮,施侣元,等.核苷酸切除修复基因表达低下与肺癌的关系[J].中国公共卫生,2003,19(7):780-782.
25. Shirota,Y,Stoehlmacher,J.,Brabender,J,,Xiong,YP,Uetake,H.,Danenberg,K.D.,Groshen,S.,Tsao-Wei,D.D.,Danenberg,EV.,and Lenz,H.J.,ERCC 1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy.JCiin Oncol,2001.19(23):P.4298—304.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |