农药毒死蜱和氯氰菊酯的遗传毒性研究
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摘要
毒死蜱(CAS编号:2921-88-2)是一种有机磷杀虫剂,其化学名称为:O,O-二乙基-O-(3,5,6-三氯-2-吡啶基)硫代磷酸酯,具杀虫活性是因为毒死蜱脱硫形成的毒死蜱氧磷使乙酰胆碱酯酶(AChE)磷酸化。磷酸化的AChE不能水解神经递质乙酰胆碱。过量的乙酰胆碱过度刺激乙酰胆碱受体,导致靶生物死亡。氯氰菊酯(CAS编号:52315-07-8)是一种拟除虫菊酯杀虫剂,其化学名称为:(RS)-a-氰基-3-苯氧苄基(1RS)-顺,反-3-(2,2-二氯乙烯基)-2,2-二甲基环丙烷羧酸酯,具杀虫活性是因为它使嵌于神经膜上的Na~+-通道持久开放,严重延迟Na~+-通道的激活、失活和去激活,引起神经细胞持续冲动,导致靶生物死亡。毒死蜱和氯氰菊酯是两种广泛使用的农药,但有关其遗传毒性的机制不很明确,本文围绕这一中心问题开展研究。
毒死蜱和氯氰菊酯均具有强疏水性。两种杀虫剂可能通过分配进入血脂和与血蛋白质结合而被运输。杀虫剂的运输直接影响其分布、代谢和排泄。白蛋白和血红蛋白是血液中两种重要的运输蛋白。杀虫剂与蛋白质结合将影响蛋白质的生理功能。为研究杀虫剂与血液蛋白质结合的特征,在1μmol/L牛血清白蛋白或牛血红蛋白溶液中,逐步注入微量的杀虫剂溶液,使杀虫剂与白蛋白或血红蛋白的摩尔比分别从0增至20或100。每次滴定后测量体系的荧光强度。采用改进的回归方法分析荧光强度的变化,计算结合常数和结合位点数。结果:两种杀虫剂均引起白蛋白荧光猝灭和血红蛋白荧光增强。毒死蜱和氯氰菊酯与白蛋白的结合常数和结合位点数分别是2.99×10~5和5.22×10~5 L/mol,1.25和0.78。毒死蜱和氯氰菊酯与血红蛋白的结合常数和结合位点数分别是2.94×10~4和2.48×10~4 L/mol,1.75和2.19。结论:毒死蜱和氯氰菊酯可与白蛋白和血红蛋白结合,两种杀虫剂与白蛋白的结合显著强于与血红蛋白的结合。
细胞色素P450(CYP)是细胞内重要的Ⅰ相代谢酶,参与物质的排泄。但是,某些P450酶如CYP1A1和3A可将前致癌物氧化为亲电性致癌物,后者可形成DNA加合物,启动癌症发生。物质增强前致癌物激活的能力称助癌性。CYP2B1和3A可产生活性氧(ROS)攻击DNA。为研究毒死蜱和氯氰菊酯对CYP活性
Chlorpyrifos (CAS No: 2921-88-2) is an organophosphorus insecticide, and its chemical name is O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl)phosphorothionate. Chlorpyrifos has insecticidal activity because chlorpyrifos-oxon, which results from desulfuration of chlorpyrifos, can phosphorylate acetylcholine esterase (AChE). The phosphorylated AChE can not hydrolyze the neurotransmitter acetylcholine. Excess acetylcholine overstimulates acetylcholine receptors, leading to the death of target organisms. Cypermethrin (CAS No: 52315-07-8) is a pyrethroid insecticide, and its chemical name is (RS)-a-cyano-3-phenoxybenzyl (1RS)-cis ,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate. Cypermethrin has insecticidal activity because it causes the sustained opening of Na~+-channels embedded in nerve membranes and severely retards the activation, inactivation, and deactivation of Na+-channels, which causes the continued impulses in neurons, leading to the death of target organisms. Chlorpyrifos and cypermethrin are two widely used pesticides, but the mechanism of their genotoxicity is not well established. The focus of present study is on the mechanism.Both chlorpyrifos and cypermethrin possess strong hydrophobicity. It is probable that both insecticides are transported to target organs through partitioning into blood lipids and binding to blood proteins. The transportation of insecticides directly affects their distribution, metabolism and excretion. Albumin and hemoglobin are two improtant transport proteins in blood. Binding of an insecticide to the proteins will affect their physiological functions. The binding of insecticide to blood proteins is characterized. A minute volume of insecticide solution is progressively injected into 1 μmol/L bovine serum albumin or bovine hemoglobin. The molar ratio of insecticide to albumin and hemoglobin increases from 0 to 20 and 100, respectively. After every titration, the fluorescence of system is determined. A modified regression is used to analyze the alteration of fluorescence and calculate the association constant and the number of binding sites. It is found that both insecticides cause fluorescence quenching of the
albumin and fluorescence enhancement of the hemoglobin. The association constant and the number of binding sites of chlorpyrifos and cypermethrin binding to the albumin are 2.99xlO5 and 5.22xlO5 L/mol, 1.25 and 0.78, respectively. The association constant and the number of binding sites of chlorpyrifos and cypermethrin binding to the hemoglobin are 2.94xlO4 and 2.48xlO4 L/mol, 1.75 and 2.19, respectively. The results indicate that chlorpyrifos and cypermethrin can- bind to albumin and hemoglobin, and the binding of insecticides to albumin is significantly stronger than that to hemoglobin.Cytochrome P450 (CYP) are the phase I enzymes of great importance in cells and involved in the excretion of substance. However, some CYP such as CYP1 Al and 3A can oxidize precarcinogen into electrophilic carcinogen, which may form DNA adducts, initiating carcinogenesls. The ability of substance to substantiate activation of precarcinogen is called cocarcinogenicity. CYP2B1 and 3A can produce reactive oxygen species (ROS) which may insult DNA. The effect of chlorpyrifos and cypermethrin on activities of CYP is studied. ICR (Institute of Cancer Research) mice are intraperitoneally administrated with chlorpyrifos (25.0, 50.0 mg/kg bw/d) or cypermethrin (100.0, 200.0 mg/kg bw/d) for 3 days. On the 4th day, the activities of CYP in liver, kidney and lung are determined. It is found that both insecticides increase activities of CYP in most cases. For example, the treatment of 50.0 mg/kg chlorpyrifos increases the activities of lung CYP1A1 of male and female mice by 86% and 62%, respectively. The treatment of 200.0 mg/kg cypermethrin increases the activities of lung CYP1A2 of female mice and kidney CYP2B1 of male mice by 109% and 69%, respectively. Both insecticides exert sex-specific influence on activities of some CYP, such as CYP1A1 in liver and kidney, CYP1A2 in kidney, CYP2E1 in liver, CYP3A in liver and lung for chlorpyrifos, and CYP1A2 in liver and lung, CYP2B1 in kidney, CYP2E1 in liver, kidney and lung for cypermethrin. Both insecticides also exert organ-specific influence on activities of some CYP, such as CYP1A1, 1A2, 2B1, 2E1 of female and male mice, CYP3A of male mice for chlorpyrifos, and CYP1A2, 2E1, 3A of female and male mice, CYP2B1 of female mice for cypermethrin. Chlorpyrifos significantly increases activities of CYP1A1 in lung, and CYP2B1 in kidney and lung. Cypermethrin significantly increases activities of CYP1A1 in liver, kidney and lung, CYP2B1 in liver and lung, and CYP3A in liver. The
results suggest that chlorpyrifos and cypermethrin have cocarcinogenicity and indirectly damage DNA through increase of reactive oxygen species (ROS) that result from the increase of CYP activities.The types of DNA damage by chlorpyrifos and cypermethrin are studied through four assays, which are performed as follows.1) Single cell gel electrophoresis (comet) assay. ICR mouse primary lymphocytes are treated with 3.1-50.0 ^g/mL chlorpyrifos or 6.3-100.0 ^wg/mL cypermethrin for 2 h. Frequency of comet cells is determined. It is found that under the treatment of PBS buffer or 1% dimethyl sulfoxide (DMSO), the frequency of comet cells is 6%. Chlorpyrifos and cypermethrin significantly increase the frequency of comet cells to 13-45% and 17-37% (P < 0.001), respectively. It is concluded that both chlorpyrifos and cypermethrin can lead to DNA strand breakage.2) Bioluminescence assay. ICR mouse primary hepatocytes are treated with 0.39-100.00 jug/mL chlorpyrifos or 0.78-200.00 /(g/mL cypermethrin for 4 h. DNA adduct coefficients are determined and DNA adduct coefficient by 1% DMSO is defined as 0. It is found that DNA adduct coefficients by chlorpyrifos are 0.01-0.53, which are not significantly different from that by 1% DMSO (P > 0.05). DNA adduct coefficients by cypermethrin are 0.71-0.90, which are significantly higher than that by 1% DMSO (P < 0.05, P < 0.01). The results illustrate that cypermethrin can lead to the formation of DNA adducts but chlorpyrifos cannot.3) K+-SDS precipitation assay. ICR mouse primary hepatocytes are treated with 0.39-100.00 jug/mL chlorpyrifos or 0.78-200.00 //g/mL cypermethrin for 4 h. DNA-protein crosslink coefficients are determined and DNA-protein crosslink coefficient by 1% DMSO is defined as 1. It is found that DNA-protein crosslink coefficients by chlorpyrifos and cypermethrin are 0.80-0.94 and 0.68-1.07, respectively, which are not significantly different from that by 1% DMSO (P > 0.05). It is concluded that neither chlorpyrifos nor cypermethrin cause DNA-protein crosslinks.4) Ethidium bromide fluorescence assay. Calf thymus DNA and ICR mouse primary hepatocytes are solely treated with 0.39-100.00 ^g/mL chlorpyrifos or 0.78-200.00 jug/mL cypermethrin for 4 h. A parallel group of hepatocytes is co-treated with insecticide
and SKF-525A, a cytochrome P450 inhibitor. The ratio (R) of DNA fluorescence intensity after denaturing to that before denaturing is calculated. It is found that under the treatment of 1% DMSO, the R of calf thymus DNA, hepatocytes, and hepatocytes co-treated with SKF-525A are 0.600, 0.608 and 0.596, respectively. Under the treatment of chlorpyrifos, the corresponding R are 0.591-0.609, 0.612-0.626, and 0.587-0.610, respectively, which are not significantly different from the corresponding R by 1% DMSO (P > 0.05). Under the treatment of cypermethrin, the R of calf thymus DNA and hepatocytes co-treated with SKF-525A are 0.586-0.592 and 0.573-0.592, respectively, which are not significantly different from the corresponding R by 1% DMSO (P > 0.05). It is worth notice that the R of hepatocytes treated with 0.78-12.50 ,Mg/mL cypermethrin increase to 0.634-0.654, which are significantly different from the corresponding R by 1% DMSO (P < 0.05, P < 0.001). However, the R of hepatocytes treated with 50.00 and 200.00 fig/mL cypermethrin decrease to the level of corresponding control. The results indicate that chlorpyrifos can not cause formation of DNA interstrand crosslinks, but cypermethrin can cause it. Active metabolites of cypermethrin instead of cypermethrin itself cause DNA interstrand crosslinks. Cytochrome P450 may be involved in the activation of cypermethrin. Cypermethrin of high concentrations may inhibit the activation of cypermethrin by cytochrome P450.DNA repair under the treatment of chlorpyrifos or cypermethrin is studied. ICR mouse primary lymphocytes and hepatocytes are treated with 3.1-50.0 //g/mL chlorpyrifos or 6.3-100.0 jug/mh cypermethrin for 3 h. The unscheduled DNA synthesis (UDS) assay is performed. It is discovered that under the treatments of PBS buffer, 1% DMSO, chlorpyrifos, and cypermethrin, the incorporations of 3H-thymidine (3H-TdR) into DNA, which is extracted from 1.6xlO6 lymphocytes, are 632, 676, 568-922, and 482-630 disintegrations/min (dpm), respectively. The corresponding incorporations of 3H-TdR into 40 n% DNA of hepatocytes are 615, 680, 344-391, and 335-553 dpm, respectively. It is displayed that the unscheduled DNA synthesis in lymphocytes or hepatocytes treated with chlorpyrifos or cypermethrin is not significantly different from that by PBS buffer or 1% DMSO (P > 0.05). The results illustrate that there is not significant DNA repair when chlorpyrifos or cypermethrin damages DNA.
DNA methylation plays an important role in the regulation of gene expression in eukaryotes. Effect of chlorpyrifos and cypermethrin on DNA methylation level is studied. ICR mouse primary hepatocytes are treated with 3.1-50.0 /ig/mL chlorpyrifos or 6.3-100.0 jug/mL cypermethrin for 4 h. High performance liquid chromatography (HPLC) is used to determine the content of DNA bases. It is found that DNA methylation levels in hepatocytes treated with PBS buffer and 1% DMSO are 62.8% and 52.2%, repectively. The levels in hepatocytes treated with chlorpyrifos and cypermethrin are 16.9-35.1% and 18.8-26.4%, repectively, which are significantly lower than that by PBS buffer or 1% DMSO (P < 0.001). The results indicate that both chlorpyrifos and cypermethrin can decrease DNA methylation levels.Since chlorpyrifos and cypermethrin can damage DNA of somatic cells, they may damage DNA of germ cells through similar mechanisms, impacting on mammalian reproduction and development. A preliminary study on reproductive toxicity of chlorpyrifos and cypermethrin is performed. ICR male mice are intraperitoneally administrated with chlorpyrifos (25.0, 50.0 mg/kg bw/d) or cypermethrin (100.0, 200.0 mg/kg bw/d) for 4 days. On 7th day, ratio of bilaterally testicular weight to body weight (i?t/b) and frequency of abnonnal sperm are determined. It is shown that the i?t/b of mice treated with corn oil is 8.49x10"3. Under the treatments of low and high doses of chlorpyrifos, and low and high doses of cypermethrin, the /?t/b are 7.93x10"3, 8.53x10"3, and 8.98x10"3, 7.88x10"', respectively, which are not significantly different from that by corn oil (P > 0.05). Frequency of abnormal sperm of mice treated with corn oil is l%o. Under the treatments of low and high doses of chlorpyrifos, or low and high doses of cypermethrin, the frequency of abnormal sperm are 40%o and 71%o, or 99%o and 125%o, respectively, which are significantly higher than that by corn oil (P < 0.001). It is illustrated that both chlorpyrifos and cypermethrin have reproductive toxicity.From the present study, two new ideas are brought forth as follows.(A) To obtain the association constant and the number of binding sites between chemical and protein, a new parameter, i.e., the fluorescence intensity of system when adequate chemical is added, is introduced in linear regression analysis. The modified method well describes both quenching and enhancement of fluorescence.
(B) The probable pathways that cypermethrin is activated are put forward. The product from hydrolysis of cypermethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid, can be hydroxylated in two ways: 1) the methyl group on cyclopropane group is hydroxylated and the product is oxidized into an epoxide, 3-(2,2-dichloro-l,2-epoxyethyl)-2-hydroxymethyl- 2-methylcyclopropanecarboxylic acid, which can form DNA monoadducts. 2) 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid is hydroxylated via rearrangement of radical and formation of carbocation, and the products are oxidized into two diepoxides: 5,5-dichloro-3-hydroxy-2-(l,2-epoxyisopropyl)-4,5-epoxypentanoic acid and5,5-dichloro-2-hydroxy-3-(l,2-epoxyisopropyl)-4,5-epoxypentanoic acid, which can cause DNA monoadducts and DNA interstrand crosslinks.
毒死蜱和氯氰菊酯均具有强疏水性。两种杀虫剂可能通过分配进入血脂和与血蛋白质结合而被运输。杀虫剂的运输直接影响其分布、代谢和排泄。白蛋白和血红蛋白是血液中两种重要的运输蛋白。杀虫剂与蛋白质结合将影响蛋白质的生理功能。为研究杀虫剂与血液蛋白质结合的特征,在1μmol/L牛血清白蛋白或牛血红蛋白溶液中,逐步注入微量的杀虫剂溶液,使杀虫剂与白蛋白或血红蛋白的摩尔比分别从0增至20或100。每次滴定后测量体系的荧光强度。采用改进的回归方法分析荧光强度的变化,计算结合常数和结合位点数。结果:两种杀虫剂均引起白蛋白荧光猝灭和血红蛋白荧光增强。毒死蜱和氯氰菊酯与白蛋白的结合常数和结合位点数分别是2.99×10~5和5.22×10~5 L/mol,1.25和0.78。毒死蜱和氯氰菊酯与血红蛋白的结合常数和结合位点数分别是2.94×10~4和2.48×10~4 L/mol,1.75和2.19。结论:毒死蜱和氯氰菊酯可与白蛋白和血红蛋白结合,两种杀虫剂与白蛋白的结合显著强于与血红蛋白的结合。
细胞色素P450(CYP)是细胞内重要的Ⅰ相代谢酶,参与物质的排泄。但是,某些P450酶如CYP1A1和3A可将前致癌物氧化为亲电性致癌物,后者可形成DNA加合物,启动癌症发生。物质增强前致癌物激活的能力称助癌性。CYP2B1和3A可产生活性氧(ROS)攻击DNA。为研究毒死蜱和氯氰菊酯对CYP活性
Chlorpyrifos (CAS No: 2921-88-2) is an organophosphorus insecticide, and its chemical name is O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl)phosphorothionate. Chlorpyrifos has insecticidal activity because chlorpyrifos-oxon, which results from desulfuration of chlorpyrifos, can phosphorylate acetylcholine esterase (AChE). The phosphorylated AChE can not hydrolyze the neurotransmitter acetylcholine. Excess acetylcholine overstimulates acetylcholine receptors, leading to the death of target organisms. Cypermethrin (CAS No: 52315-07-8) is a pyrethroid insecticide, and its chemical name is (RS)-a-cyano-3-phenoxybenzyl (1RS)-cis ,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate. Cypermethrin has insecticidal activity because it causes the sustained opening of Na~+-channels embedded in nerve membranes and severely retards the activation, inactivation, and deactivation of Na+-channels, which causes the continued impulses in neurons, leading to the death of target organisms. Chlorpyrifos and cypermethrin are two widely used pesticides, but the mechanism of their genotoxicity is not well established. The focus of present study is on the mechanism.Both chlorpyrifos and cypermethrin possess strong hydrophobicity. It is probable that both insecticides are transported to target organs through partitioning into blood lipids and binding to blood proteins. The transportation of insecticides directly affects their distribution, metabolism and excretion. Albumin and hemoglobin are two improtant transport proteins in blood. Binding of an insecticide to the proteins will affect their physiological functions. The binding of insecticide to blood proteins is characterized. A minute volume of insecticide solution is progressively injected into 1 μmol/L bovine serum albumin or bovine hemoglobin. The molar ratio of insecticide to albumin and hemoglobin increases from 0 to 20 and 100, respectively. After every titration, the fluorescence of system is determined. A modified regression is used to analyze the alteration of fluorescence and calculate the association constant and the number of binding sites. It is found that both insecticides cause fluorescence quenching of the
albumin and fluorescence enhancement of the hemoglobin. The association constant and the number of binding sites of chlorpyrifos and cypermethrin binding to the albumin are 2.99xlO5 and 5.22xlO5 L/mol, 1.25 and 0.78, respectively. The association constant and the number of binding sites of chlorpyrifos and cypermethrin binding to the hemoglobin are 2.94xlO4 and 2.48xlO4 L/mol, 1.75 and 2.19, respectively. The results indicate that chlorpyrifos and cypermethrin can- bind to albumin and hemoglobin, and the binding of insecticides to albumin is significantly stronger than that to hemoglobin.Cytochrome P450 (CYP) are the phase I enzymes of great importance in cells and involved in the excretion of substance. However, some CYP such as CYP1 Al and 3A can oxidize precarcinogen into electrophilic carcinogen, which may form DNA adducts, initiating carcinogenesls. The ability of substance to substantiate activation of precarcinogen is called cocarcinogenicity. CYP2B1 and 3A can produce reactive oxygen species (ROS) which may insult DNA. The effect of chlorpyrifos and cypermethrin on activities of CYP is studied. ICR (Institute of Cancer Research) mice are intraperitoneally administrated with chlorpyrifos (25.0, 50.0 mg/kg bw/d) or cypermethrin (100.0, 200.0 mg/kg bw/d) for 3 days. On the 4th day, the activities of CYP in liver, kidney and lung are determined. It is found that both insecticides increase activities of CYP in most cases. For example, the treatment of 50.0 mg/kg chlorpyrifos increases the activities of lung CYP1A1 of male and female mice by 86% and 62%, respectively. The treatment of 200.0 mg/kg cypermethrin increases the activities of lung CYP1A2 of female mice and kidney CYP2B1 of male mice by 109% and 69%, respectively. Both insecticides exert sex-specific influence on activities of some CYP, such as CYP1A1 in liver and kidney, CYP1A2 in kidney, CYP2E1 in liver, CYP3A in liver and lung for chlorpyrifos, and CYP1A2 in liver and lung, CYP2B1 in kidney, CYP2E1 in liver, kidney and lung for cypermethrin. Both insecticides also exert organ-specific influence on activities of some CYP, such as CYP1A1, 1A2, 2B1, 2E1 of female and male mice, CYP3A of male mice for chlorpyrifos, and CYP1A2, 2E1, 3A of female and male mice, CYP2B1 of female mice for cypermethrin. Chlorpyrifos significantly increases activities of CYP1A1 in lung, and CYP2B1 in kidney and lung. Cypermethrin significantly increases activities of CYP1A1 in liver, kidney and lung, CYP2B1 in liver and lung, and CYP3A in liver. The
results suggest that chlorpyrifos and cypermethrin have cocarcinogenicity and indirectly damage DNA through increase of reactive oxygen species (ROS) that result from the increase of CYP activities.The types of DNA damage by chlorpyrifos and cypermethrin are studied through four assays, which are performed as follows.1) Single cell gel electrophoresis (comet) assay. ICR mouse primary lymphocytes are treated with 3.1-50.0 ^g/mL chlorpyrifos or 6.3-100.0 ^wg/mL cypermethrin for 2 h. Frequency of comet cells is determined. It is found that under the treatment of PBS buffer or 1% dimethyl sulfoxide (DMSO), the frequency of comet cells is 6%. Chlorpyrifos and cypermethrin significantly increase the frequency of comet cells to 13-45% and 17-37% (P < 0.001), respectively. It is concluded that both chlorpyrifos and cypermethrin can lead to DNA strand breakage.2) Bioluminescence assay. ICR mouse primary hepatocytes are treated with 0.39-100.00 jug/mL chlorpyrifos or 0.78-200.00 /(g/mL cypermethrin for 4 h. DNA adduct coefficients are determined and DNA adduct coefficient by 1% DMSO is defined as 0. It is found that DNA adduct coefficients by chlorpyrifos are 0.01-0.53, which are not significantly different from that by 1% DMSO (P > 0.05). DNA adduct coefficients by cypermethrin are 0.71-0.90, which are significantly higher than that by 1% DMSO (P < 0.05, P < 0.01). The results illustrate that cypermethrin can lead to the formation of DNA adducts but chlorpyrifos cannot.3) K+-SDS precipitation assay. ICR mouse primary hepatocytes are treated with 0.39-100.00 jug/mL chlorpyrifos or 0.78-200.00 //g/mL cypermethrin for 4 h. DNA-protein crosslink coefficients are determined and DNA-protein crosslink coefficient by 1% DMSO is defined as 1. It is found that DNA-protein crosslink coefficients by chlorpyrifos and cypermethrin are 0.80-0.94 and 0.68-1.07, respectively, which are not significantly different from that by 1% DMSO (P > 0.05). It is concluded that neither chlorpyrifos nor cypermethrin cause DNA-protein crosslinks.4) Ethidium bromide fluorescence assay. Calf thymus DNA and ICR mouse primary hepatocytes are solely treated with 0.39-100.00 ^g/mL chlorpyrifos or 0.78-200.00 jug/mL cypermethrin for 4 h. A parallel group of hepatocytes is co-treated with insecticide
and SKF-525A, a cytochrome P450 inhibitor. The ratio (R) of DNA fluorescence intensity after denaturing to that before denaturing is calculated. It is found that under the treatment of 1% DMSO, the R of calf thymus DNA, hepatocytes, and hepatocytes co-treated with SKF-525A are 0.600, 0.608 and 0.596, respectively. Under the treatment of chlorpyrifos, the corresponding R are 0.591-0.609, 0.612-0.626, and 0.587-0.610, respectively, which are not significantly different from the corresponding R by 1% DMSO (P > 0.05). Under the treatment of cypermethrin, the R of calf thymus DNA and hepatocytes co-treated with SKF-525A are 0.586-0.592 and 0.573-0.592, respectively, which are not significantly different from the corresponding R by 1% DMSO (P > 0.05). It is worth notice that the R of hepatocytes treated with 0.78-12.50 ,Mg/mL cypermethrin increase to 0.634-0.654, which are significantly different from the corresponding R by 1% DMSO (P < 0.05, P < 0.001). However, the R of hepatocytes treated with 50.00 and 200.00 fig/mL cypermethrin decrease to the level of corresponding control. The results indicate that chlorpyrifos can not cause formation of DNA interstrand crosslinks, but cypermethrin can cause it. Active metabolites of cypermethrin instead of cypermethrin itself cause DNA interstrand crosslinks. Cytochrome P450 may be involved in the activation of cypermethrin. Cypermethrin of high concentrations may inhibit the activation of cypermethrin by cytochrome P450.DNA repair under the treatment of chlorpyrifos or cypermethrin is studied. ICR mouse primary lymphocytes and hepatocytes are treated with 3.1-50.0 //g/mL chlorpyrifos or 6.3-100.0 jug/mh cypermethrin for 3 h. The unscheduled DNA synthesis (UDS) assay is performed. It is discovered that under the treatments of PBS buffer, 1% DMSO, chlorpyrifos, and cypermethrin, the incorporations of 3H-thymidine (3H-TdR) into DNA, which is extracted from 1.6xlO6 lymphocytes, are 632, 676, 568-922, and 482-630 disintegrations/min (dpm), respectively. The corresponding incorporations of 3H-TdR into 40 n% DNA of hepatocytes are 615, 680, 344-391, and 335-553 dpm, respectively. It is displayed that the unscheduled DNA synthesis in lymphocytes or hepatocytes treated with chlorpyrifos or cypermethrin is not significantly different from that by PBS buffer or 1% DMSO (P > 0.05). The results illustrate that there is not significant DNA repair when chlorpyrifos or cypermethrin damages DNA.
DNA methylation plays an important role in the regulation of gene expression in eukaryotes. Effect of chlorpyrifos and cypermethrin on DNA methylation level is studied. ICR mouse primary hepatocytes are treated with 3.1-50.0 /ig/mL chlorpyrifos or 6.3-100.0 jug/mL cypermethrin for 4 h. High performance liquid chromatography (HPLC) is used to determine the content of DNA bases. It is found that DNA methylation levels in hepatocytes treated with PBS buffer and 1% DMSO are 62.8% and 52.2%, repectively. The levels in hepatocytes treated with chlorpyrifos and cypermethrin are 16.9-35.1% and 18.8-26.4%, repectively, which are significantly lower than that by PBS buffer or 1% DMSO (P < 0.001). The results indicate that both chlorpyrifos and cypermethrin can decrease DNA methylation levels.Since chlorpyrifos and cypermethrin can damage DNA of somatic cells, they may damage DNA of germ cells through similar mechanisms, impacting on mammalian reproduction and development. A preliminary study on reproductive toxicity of chlorpyrifos and cypermethrin is performed. ICR male mice are intraperitoneally administrated with chlorpyrifos (25.0, 50.0 mg/kg bw/d) or cypermethrin (100.0, 200.0 mg/kg bw/d) for 4 days. On 7th day, ratio of bilaterally testicular weight to body weight (i?t/b) and frequency of abnonnal sperm are determined. It is shown that the i?t/b of mice treated with corn oil is 8.49x10"3. Under the treatments of low and high doses of chlorpyrifos, and low and high doses of cypermethrin, the /?t/b are 7.93x10"3, 8.53x10"3, and 8.98x10"3, 7.88x10"', respectively, which are not significantly different from that by corn oil (P > 0.05). Frequency of abnormal sperm of mice treated with corn oil is l%o. Under the treatments of low and high doses of chlorpyrifos, or low and high doses of cypermethrin, the frequency of abnormal sperm are 40%o and 71%o, or 99%o and 125%o, respectively, which are significantly higher than that by corn oil (P < 0.001). It is illustrated that both chlorpyrifos and cypermethrin have reproductive toxicity.From the present study, two new ideas are brought forth as follows.(A) To obtain the association constant and the number of binding sites between chemical and protein, a new parameter, i.e., the fluorescence intensity of system when adequate chemical is added, is introduced in linear regression analysis. The modified method well describes both quenching and enhancement of fluorescence.
(B) The probable pathways that cypermethrin is activated are put forward. The product from hydrolysis of cypermethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid, can be hydroxylated in two ways: 1) the methyl group on cyclopropane group is hydroxylated and the product is oxidized into an epoxide, 3-(2,2-dichloro-l,2-epoxyethyl)-2-hydroxymethyl- 2-methylcyclopropanecarboxylic acid, which can form DNA monoadducts. 2) 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid is hydroxylated via rearrangement of radical and formation of carbocation, and the products are oxidized into two diepoxides: 5,5-dichloro-3-hydroxy-2-(l,2-epoxyisopropyl)-4,5-epoxypentanoic acid and5,5-dichloro-2-hydroxy-3-(l,2-epoxyisopropyl)-4,5-epoxypentanoic acid, which can cause DNA monoadducts and DNA interstrand crosslinks.
引文
[1] 胡笑形.2003年世界农药工业面观(上).世界农药,2004,26(4):1—5.
[2] 敖聪聪.2003年世界销售过亿美元的农药品种.新农药,2005,(4):51-52.
[3] 束放,邵振润.2003年我国农药械市场概况与2004年农约械市场需求分析与展望.农约科学与管理,2004,25(2):34-36.
[4] 中华人民共和国农业部.中国农业信息网2003年数据资料,http://www.agri.gov.cn/sizl/2003/23.htm.
[5] C. Bolognesi, G. Morasso. Genotoxicity of pesticides: potential risk for consumers. Trends in Food Science & Technology, 2000, 11(5): 182-187.
[6] C. Bolognesi. Genotoxicity of pesticides: a review of human biomonitoring studies. Mutation Research, 2003, 543(3): 251-272.
[7] 张大宝.遗传毒性与疾病.见:印木泉,主编.遗传毒理学.北京:科学出版社,2002.p:353-356.
[8] M. Schneider, G. B. Quistad, J. E. Casida. Glutathione activation of chloropicrin in the Salmonella mutagenicity test. Mutation Research, 1999, 439(2): 233-238.
[9] J. Blasiak, P. Jaloszynski, A. Trzeciak, K. Szyfter. In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues. Mutation Research, 1999, 445(2): 275-283.
[10] 孙运光.有机磷农药的遗传毒性研究.国外医学卫生学分册,2000,27(6):349-352.
[11] 谈伟君,王心如,徐锡坤.八氯二丙醚对DNA交联作用的研究.铁道医学,1999,27(6):386-387.
[12] 刘贤德,程伟.除草剂精克草能对黄鳝的遗传毒性及二种物质的抑制作用.徐州师范大学学报(自然科学版),2000,18(2):56-58.
[13] J. Blasiak, D. Stan kowska. Genotoxicity of Malaoxon: Induction of oxidized and methylated bases and protective effect of α-tocopherol. Pesticide Biochemistry and Physiology, 2001, 71(2): 88-96.
[14] L. -E. Okoumassoun, D. Averill-Bates, M. Marion, F. Denizeau. Possible mechanisms underlying the mitogenic action of heptachlor in rat hepatocytes. Toxicology and Applied Pharmacology, 2003, 193(3): 356—369.
[15] T. J. Schrader, B. G. Boyes, T. I. Matula, C. Heroux-Metcalf, I. Langlois, R. H. Downie. In vitro investigation of toxaphene genotoxicity in S. typhimurium and Chinese hamster V79 lung fibroblasts. Mutation Research, 1998, 413(2): 159-168.
[16] C. H. Sierra-Torres, N. Cajas-Salazar, L. S. Hoyos, M. Zuleta, E. B. Whorton, W. W. Au. In vitro and in vivo genotoxic activity of miral, an organophosphorus insecticide used in Colombia. Mutation Research, 1998, 415(1): 59-67.
[17] M. J. Ruiz, D. Marzin. Genotoxicity of six pesticides by Salmonella mutagenicity test and SOS chromotest. Mutation Research, 1997, 390(3): 245-255.
[18] P. Das, G. John. Induction of sister chromatid exchanges and chromosome aberrations in vivo in Etroplus suratensis (Bloch) following exposure to organophosphorus pesticides. Toxicology Letters, 1999, 104(2): 111-116.
[19] C. Vigreux, J. M. Poul, E. Deslandes, P. Lebailly, T. Godard, F. Sichel, M. Henry-Amar, P. Gauduchon. DNA damaging effects of pesticides measured by the single cell gel electrophoresis assay (comet assay) and the chromosomal aberration test, in CHOK1 cells. Mutation Research, 1998, 419(2): 79-90.
[20] M. B. Lioi, M. R. Scarfi, A. Santoro, R. Barbieri, O. Zeni, D. Di Berardino, M. V. Ursini. Genotoxicity and oxidative stress induced by pesticide exposure in bovine lymphocyte cultures in vitro. Mutation Research, 1998, 403(1): 13-20.
[21] 谢志浩,蔡亚非,陈国,黄剑锋,余红卫.利用泥鳅红细胞微核及核异常测定法对四种除草剂遗传毒性的研究.现代农约,2002,(4):24-27.
[22] 耿德贵,张大生,程伟,陈刚,温洪宇.四种除草剂对中华大蟾蜍蝌蚪红细胞微核及核异常的影响.动物学杂志,2000,35(1):12-16.
[23] J. Surralles, N. Xamena, A. Creus, R. Marcos. Conversion of DNA adducts induced by pesticides and model mutagens to micronuclei in human lymphocytrs as new biomarker of excision repair. Mutation Research, 1995, 335(1): 77-78.
[24] A. Laouedj, C. Cschenk, A. Pfohl-leszkowicz, G. Keith, D. Schontz, P. Guillernaut, B. Dether. Detection of DNA adducts in declining hop plants grown on fields formerly treated with heptachlor, a persistent insecticide. Environmental Pollution, 1995, 90(3): 409-414.
[25] 石进元,王海芳,吴小红,李新松,刘元方,李坤,鲁向阳,汪建军,刘克新.用加速器质谱法研究低剂量抗蚜威的基因毒性.科学通报,1997,42(15):1675-1677.
[26] M. F. Rahman, M. Mahboob, K. Danadevi, B. S. Banu, P. Grover. Assessment of genotoxic effects of chloropyriphos and acephate by the comet assay in mice leucocytes. Mutation Research, 2002, 516(2): 139-147.
[27] S. Soloneski, M. Gonzalez, E. Piaggio, M.A. Reigosa, M. L. Larramendy. Effect of dithiocarbamate pesticide zineb and its commercial formulation, azzurro Ⅲ. Genotoxic evaluation on Chinese hamster ovary (CHO) cells. Mutation Research, 2002, 514(2): 201-212.
[28] 许丹倩.毒死蜱及其中间体的合成述评.浙江化工,1995,26(1):4-8.
[29] 中华人民共利国农业部农药检定所.中国农约信息网数据中心,http://www.chinapesticide.gov.cn/sjzx/yxcf.htm.
[30] J. L. Schardein, A. R. Scialli. The legislation of toxicologic safety factors: the food quality protection act with chlorpyrifos as a test case. Reproductive Toxicology, 1999, 13(1): 1-14.
[31] J. O. Lalah, D. Ondieki, S. O. Wandiga, I. O. Jumba. Dissipation, distribution, and uptake of ~(14)c-chlorpyrifos in a model tropical seawater/sediment/fish ecosystem. Bulletin of Environmental Contamination and Toxicology, 2003, 70: 883-890.
[32] R. C. Cochran. Appraisal of risks from nonoccupational exposure to chlorpyrifos. Regulatory Toxicology and Pharmacology, 2002, 35 (1): 105-121.
[33] 林郁,主编.农约应用大全.北京:农业出版社,1989.p:187,237.
[34] 吴慧明,魏方林,楼建晴,朱国念.毒死蜱的水解研究.宁波高等专科学校学报.2001,13(Sup):101-104.
[35] B. Liu, L. L. McConnell, A. Torrents. Hydrolysis of chlorpyrifos in natural waters of the Chesapeake Bay. Chemosphere, 2001, 44(6): 1315-1323.
[36] 唐除痴.杀虫剂及其他动物害物防治剂.见:唐除痴,李煜昶,陈彬,杨华铮,金桂玉,合编.农药化学.天津:南开大学出版社,1998.p:79,211.
[37] 岳永德,汤锋,花日茂,关伟,涂永志.混合农约及表面活性剂对毒死蜱光解影响的研究.安徽农业大学学报,2000,27(1):1-4.
[38] 吴慧明,朱国念.毒死蜱在灭菌和未灭菌土壤中的降解研究.农药学学报,2003,5(4):65-69.
[39] 施海萍,陈謇,叶建人.毒死蜱、乐果在大棚和露地青菜上的降解动态.浙江农业科学, 2002,(4):191-192.
[40] 范志金,刘丰茂,钱传范.氯氰菊酯的名称和组成及其光学异构体.农约科学与管理,1999,20(2):9-11,17.
[41] 俞明兴.新法合成氯氰菊酯的研究.安徽大学学报(自然科学版),1992,16(4):69-72.
[42] T. J. Smith, D. M. Soderlund. Potent actions of the pyrethroid insecticides cismethrin and cypermethrin on rat tetrodotoxin-resistant peripheral nerve (SNS/PN3) sodium channels expressed in Xenopus oocytes. Pesticide Biochemistry and Physiology, 2001, 70(1): 52-61.
[43] 夏会龙,陈宗懋.氯氰菊酯和马拉硫磷农约的水解动力学研究.农业环境保护,1989,8(5):1-3.
[44] 花日茂,岳永德,汤锋,李学德,樊德方.4种农约对3种拟菊酯杀虫剂在不同光源下的光解效应.中国环境科学,1997,17(1):72-75.
[45] 秦曙,乔雄梧,朱九生,王静.实验室条件下氯氰菊酯在土壤中的降解.农药学学报,2000,2(3):68-73.
[46] 商博,王洪涛,彭全民.三种农药在不同作物上残留动态的研究.农药,1990,29(3):31-32.
[47] 孙建析,沈芸芝,乐俊仪,杨校华.毒死蜱大鼠亚慢性毒性试验.浙江省医学科学院学报,1998,9(1):11-13.
[48] A. Goel, V. Dani, D. K. Dhawan. Protective effects of zinc on lipid peroxidation, antioxidant enzymes and hepatic: histoarchitecture in chlorpyrifos-induced toxicity. Chemico-Biological Interactions, 2005, 156(2-3): 131-140.
[49] J. T. Auman, F. J. Seidler, T. A. Slotkin. Neonatal chlorpyrifos exposure targets multiple proteins governing the hepatic adenylyl cyclase signaling cascade: implications for neurotoxicity. Developmental Brain Research, 2000, 121 (1): 19-27.
[50] R. A. Schuh, P. J. Lein, R. A. Beckles, D. A. Jett. Noncholinesterase mechanisms of chlorpyrifos neurotoxicity: altered phosphorylation of Ca~(2+)/cAMP response element binding protein in cultured neurons. Toxicology and Applied Pharmacology, 2002, 182(2): 176-185.
[51] J. A. Bomser, G. B. Quistad, J. E. Casida. Chlorpyrifos oxon potentiates diacylglycerol-induced extracellular signal-regulated kinase (ERK 44/42) activation, possibly by diacylglycerol lipase inhibition. Toxicology and Applied Pharmacology, 2002, 178(1): 29-36.
[52] M. Ghisari, E. C. Bonefeld-Jorgensen. Impact of environmental chemicals on the thyroid hormone function in pituitary rat GH3 cells. Molecular and Cellular Endocrinology, 2005, 244(1): 31-41.
[53] H.R. Andersen, A.M. Vinggaard, T.H. Rasmussen, I.M. Gjermandsen, E.C. Bonefeld-Jorgensen. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Toxicology and Applied Pharmacology, 2002, 179(1): 1-12.
[54] H.T. Grunfeld, E.C. Bonefeld-Jorgensen. Effect of in vitro estrogenic pesticides on human oestrogen receptor a and ft mRNA levels. Toxicology Letters, 2004, 151(3): 467-480
[55] A.T. Farag, A.M. El Okazy, A.F. El-Aswed. Developmental toxicity study of chlorpyrifos in rats. Reproductive Toxicology, 2003, 17(2): 203-208.
[56] Y. Tian, H. Ishikawa, T. Yamaguchi, T. Yamauchi, K. Yokoyama. Teratogenicity and developmental toxicity of chlorpyrifos: maternal exposure during organogenesis in mice. Reproductive Toxicology, 2005, 20(2): 267-271.
[57] H.A. Navarro, P.V. Basta, F.J. Seidler, T.A. Slotkin. Neonatal chlorpyrifos administration elicits deficits in immune function in adulthood: a neural effect? Developmental Brain Research, 2001, 130(2): 249-252.
[58] K.P. Das, S. Barone Jr. Neuronal differentiation in PC12 cells is inhibited by chlorpyrifos and its metabolites: is acetylcholinesterase inhibition the site of action? Toxicology and Applied Pharmacology, 1999, 160(3): 217-230.
[59] A.S. Howard, R. Bucelli, D.A. Jett, D. Bruun, D. Yang, P.J. Lein. Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures. Toxicology and AppliedPharmacology, 2005, 207(2): 112-124.
[60] M.-G. Zurich, P. Honegger, B. Schilter, L.G. Costa, F. Monnet-Tschudi. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos. Toxicology and Applied Pharmacology, 2004, 201 (2): 97-104.
[61] S.J. Garcia, F.J. Seidler, D. Qiao, T.A. Slotkin. Chlorpyrifos targets developing glia: effects on glial fibrillary acidic protein. Developmental Brain Research, 2002, 133(2): 151-161.
[62] M. Guizzetti, S. Pathak, G. Giordano, L.G. Costa. Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation. Toxicology, 2005, 215(3): 182-190.
[63] T.A. Slotkin, F.J. Seidler. The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent. Developmental Brain Research, 2005, 158(1-2): 115-119.
[64] K..W. Raines, F.J. Seidler, T.A. Slotkin. Alterations in serotonin transporter expression in brain regions of rats exposed neonatally to chlorpyrifos. Developmental Brain Research, 2001, 130(1): 65-72.
[65] T. A. Slotkin, C. A. Tate, M. M. Cousins, F. J. Seidler. Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure. Developmental Brain Research, 2002, 133(2): 163-173.
[66] K. Dam, F. J. Seidler, T. A. Slotkin. Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration. Developmental Brain Research, 1998, 108(1-2): 39-45.
[67] T. L. Crumpton, F. J. Seidler, T. A. Slotkin. Developmental neurotoxicity of chlorpyrifos in vivo and in vitro: effects on nuclear transcription factors involved in cell replication and differentiation. Brain Research, 2000, 857(1-2): 87-98.
[68] K. Dam, F. J. Seidler, T. A. Slotkin. Transcriptional biomarkers distinguish between vulnerable periods for developmental neurotoxicity of chlorpyrifos: implications for toxicogenomics. Brain Research Bulletin, 2003, 59(4): 261-265.
[69] T. L. Crumpton, F. J. Seidler, T. A. Slotkin. Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos? Developmental Brain Research, 2000, 121(2): 189-195.
[70] D. K. Parran, G. Magnin, W. Li, B. S. Jortner, M. Ehrich. Chlorpyrifos alters functional integrity and structure of an in vitro BBB model: co-cultures of bovine endothelial cells and neonatal rat astrocytes. Neuro Toxicology, 2005, 26(1): 77-88.
[71] K. Dam, F. J. Seidler, T. A. Slotkin. Chlorpyrifos releases norepinephrine from adult and neonatal rat brain synaptosomes. Developmental Brain Research, 1999, 118(1-2): 129-133.
[72] J. R. Bloomquist, R. L. Barlow, J. S. Gillette, W. Li, M. L. Kirby. Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways. Neuro Toxicology, 2002, 23(4-5): 537-544.
[73] C. J. Gordon, B. K. Padnos. Prolonged elevation in blood pressure in the unrestrained rat exposed to chlorpyrifos. Toxicology, 2000, 146(1): 1-13.
[74] 李寿祺,刘玉清,倪祖尧,宋晓鸥,刘晓蓉,赵林.24种有机磷农药的诱变性.中国药理学与毒理学杂志,1993,7(1):73-77.
[75] B. B. Gollapudi, A. L. Mendrala, V. A. Linscombe. Evaluation of the genetic toxicity of the organophosphate insecticide chlorpyrifos. Mutation Research, 1995, 342(1-2): 25-36.
[76] 宋晓鸥,林凡,姜幼纯,刘晓蓉,张培厚,刘玉清.19种有机磷农约对酵母D61.M菌株的 诱变性.中国药理学与毒理学杂志,1997,11(4):291-293.
[77] Y. Tian, T. Yamauchi. Micronucleus formation in 3-day mouse embryos associated with maternal exposure to chlorpyrifos during the early preimplantation period. Reproductive Toxicology, 2003, 17(4): 401-405.
[78] B. Dimitrov, P. Gadeva. Genotoxicity studies on the insecticide dursban in root meristem cells of Crepis capillaris L.. Environmental and Experimental Botany, 1997, 37(2-3): 199-209.
[79] 刘永霞,张树来,史岩,谢琳.农药氯氰菊酯的毒性实验.职业与健康,2003,19(6):37-38.
[80] B. Giray, A. Gürbay, F. Hincal. Cypermethrin-induced oxidative stress in rat brain and liver is prevented by Vitamin E or allopurinol. Toxicology Letters, 2001, 118(3): 139-146.
[81] M. Kale, N. Rathore, S. John, D. Bhatnagar. Lipid peroxidative damage on pyrethroid exposure and alterations in antioxidant status in rat erythrocytes: a possible involvement of reactive oxygen species. Toxicology Letters, 1999, 105(3): 197-205.
[82] R. Gabbianelli, G. Falcioni, C. Nasuti, F. Cantalamessa. Cypermethrin-induced plasma membrane perturbation on erythrocytes from rats: reduction of fluidity in the hydrophobic core and in glutathione peroxidase activity. Toxicology, 2002, 175(1-3): 91-101.
[83] P. Grajeda-Cota, M. V. Ramirez-Mares, E. G. de Mejia. Vitamin C protects against in vitro cytotoxicity of cypermethrin in rat hepatocytes. Toxicology in Vitro, 2004, 18(1): 13-19.
[84] L. Aldana, E. G. de Mejia, A. Craigmill, V. Tsutsumi, J. Armendariz-Borunda, A. Panduro, A. R. Rincon. Cypermethrin increases apo A-1 and apo B mRNA but not hyperlipidemia in rats. Toxicology Letters, 1998, 95(1): 31-39.
[85] 夹访贤,张秀莲,于丽华.氯氰菊酯对大鼠肝线粒体、微粒体钙离子转运的影响.中国公共卫生学报,1994,13(5):257-259.
[86] 张秀莲,夹访贤,于丽华.拟除虫菊酯类农约对大鼠肝线粒体、微粒体Ca(2+)-ATP酶活力的影响.中国公共卫生学报,1994,13(5):303-305.
[87] 夹访贤,张秀莲,于丽华.氯氰菊酯对大鼠肝脏磷酸化酶a、Ca~(2+)-ATP酶活力的影响.中国公共卫生学报,1995,14(2):88-89.
[88] 张秀莲,夹访贤,于丽华,菅向东,王海石.除虫菊酯类农药对大鼠肝线粒体、微粒体~(45)Ca摄取的影响.中华劳动卫生职业病杂志,1997,15(5):258-260.
[89] G. de Sousa, F. Fontaine, M. Pralavorio, D. Botta-Fridlund, Y. Letreut, R. Rahmani. Insecticide cytotoxicity and CYP1A1/2 induction in primary human and rat hepatocyte cultures. Toxicology in Vitro, 1997, 11(5): 451—457.
[90] A. F. Heder, K. I. Hirsch-Ernst, D. Bauer, G. F. Kahl, H. Desel. Induction of cytochrome P450 2B1 by pyrethroids in primary rat hepatocyte cultures. Biochemical Pharmacology, 2001, 62(1): 71-79.
[91] K. S. El-Gendy, N. M. Aly, E. Rashwaan, A. H. El-Sebae. Biochemical targets affected by sublethal doses of cypermethrin. Toxicology Letters, 1998, 95 (Supplement 1): 143.
[92] L. Instit6ris, O. Siroki, U. Undeger, I. Desi, L. Nagymajtenyi. Immunotoxicological effects of repeated combined exposure by cypermethrin and the heavy metals lead and cadmium in rats. International Journal of lmmunopharmacology, 1999, 21(11): 735-743.
[93] L. Institoris, U. Undeger, O. Siroki, M. Nehez, I. Desi. Comparison of detection sensitivity of immuno- and genotoxicological effects of subacute cypermethrin and permethrin exposure in rats. Toxicology. 1999, 137(1): 47-55.
[94] 童建,朱本兴,王道锦.氯氰菊酯对淋巴细胞信使昼夜节律的影响.卫生毒理学杂志,1997,11(3):144-147.
[95] 陈海热,王心如,肖继皋,胡刚,宋玲,王守林,何凤生.有机磷与拟除虫菊酯农药的拟雌激素活性研究.中华劳动卫生职业病杂志,2001,19(4):274-277.
[96] G. Santoni, F. Cantalamessa, L. Mazzucca, S. Romagnoli, M. Piccoli. Prenatal exposure to cypermethrin modulates rat NK cell cytotoxic functions. Toxicology, 1997, 120(3): 231-242.
[97] G. Santoni, F. Cantalamessa, R. Cavagna, S. Romagnoli, E. Spreghini, M. Piccoli. Cypermethrin-induced alteration of thymocyte distribution and functions in prenatally-exposed rats. Toxicology, 1998, 125(1): 67-78.
[98] F. Cantalamessa, P. Barili, R. Cavagna, M. Sabbatini, G. Tenore, F. Amenta. Influence of neonatal treatment with the pyrethroid insecticide cypermethrin on the development of dopamine receptors in the rat kidney. Mechanisms of Ageing and Development, 1998, 103(2): 165-178.
[99] A. Gupta, A. K. Agarwal, G. S. Shukla. Effect of quinalphos and cypermethrin exposure on developing blood-brain barrier: role of nitric oxide. Environmental Toxicology and Pharmacology, 2000, 8(2): 73-78.
[100] 1. Kakko, T. Toimela, H. Tahti. The toxicity of pyrethroid compounds in neural cell cultures studied with total ATP, mitochondrial enzyme activity and microscopic photographing. Environmental Toxicology and Pharmacology, 2004, 15(2-3): 95-102.
[101] I. Kakko, T. Toimela, H. Tahti. The synaptosomal membrane bound ATPase as a target for the neurotoxic effects of pyrethroids, permethrin and cypermethrin. Chemosphere, 2003, 51(6): 475-480.
[102] G. V. Rao, K. S. J. Rao. Modulation of K~+ transport across synaptosomes of rat brain by synthetic pyrethroids. Journal of the Neurological Sciences, 1997, 147(2): 127-133.
[103] 吴建平,夏若寒,石年,刘毓谷.拟除虫菊酯对大鼠脑突触体谷氨酸摄取功能的影响.卫生研究,1999,28(5):261-262.
[104] 吴建平,卢春,干英,祝卫国,夏若寒,石年,刘毓谷.拟除虫菊酯对大鼠中枢谷氨酸和γ-氨基丁酸递质影响的免疫组织化学研究.南京医科大学学报,1999,19(6):450-453.
[105] 吴建平,夏若寒,石年,刘毓谷.氯氰菊酯诱导大鼠中枢一氧化氮合酶表达增强.南京医科大学学报,1999,19(5):357-359.
[106] M. Condes-Lara, A. Graff-Guerrero, L. Vega-Riveroll. Effects of cyperrnethrin on the electroencephalographic activity of the rat: a model of chemically induced seizures. Neurotoxicology and Teratology, 1999, 21(3): 293-298.
[107] L. K. S. Chauhan, P. N. Saxena, S. K. Gupta. Cytogenetic effects of cypermethrin and fenvalerate on the root meristem cells of Allium cepa. Environmental and Experimental Botany, 1999, 42(3): 181-189.
[108] J. Surralles, N. Xamena, A. Creus, J. Catalan, H. Norppa, R. Marcos. Induction of micronuclei by five pyrethroid insecticides in whole blood and isolated human lymphocyte cultures. Mutation Research, 1995, 341 (3): 169-184.
[109] 陆肇红,童建,朱金华.氯氰菊酯微核率的时间效应.苏州医学院学报,1995,15(5):836—837.
[110] L. K. S. Chauhan, D. K. Agarwal, V. Sundararaman. In vivo induction of sister chromatid exchange in mouse bone marrow following oral exposure to commercial formulations of alpha-cyano pyrethroids. Toxicology Letters, 1997, 93(2-3): 153-157.
[111] Y. Shukla, A. Yadav, A,. Arora. Carcinogenic and cocarcinogenic potential of cypermethrin on mouse skin. Cancer Letters, 2002, 182(1): 33-41.
[112] S. F. Donovan, M. C. Pescatore. Method for measuring the logarithm of the octanol-water partition coefficient by using short octadecyl-poly(vinyl alcohol) high-performance liquid chromatography columns. Journal of Chromatography A, 2002, 952(1-2): 47-61.
[113] 马贵斌,杨频.荧光法研究维生素B_6和芦丁与白蛋白的相互作用.生物化学与生物物理进展,1990,17(4):290-295.
[114] D. Silva, C. M. Cortez, J. Cunha-Bastos, S. R. W. Louro. Methyl parathion interaction with human and bovine serum albumin. Toxicology Letters, 2004, 147(1): 53-61.
[115] 杨斌盛,杨频.人血清白蛋白与金属离子作用的荧光光谱研究.生物化学与生物物理进展,1992,19(2):110-114.
[116] R. Jaiswal, M. A. Khan, J. Musarrat. Photosensitized paraquat-induced structural alterations and free radical mediated fragmentation of serum albumin. Journal of Photochemistry and Photobiology B: Biology, 2002, 67(3): 163-170.
[117] 查冠林.细胞毒理学血细胞学基础.见:刘国廉,主编.细胞毒理学.北京:军事医学科学出版社,2001.p:236-269.
[118] 黄淑萍,陈亮,李玉红.比较与研究金属离子与三种蛋白的配位机理.光谱学与光谱分析,1995,15(5):85-89.
[119] 常希俊,杨芳,张莉,王邃.牛血红蛋白与镝(Ⅲ)、钛(Ⅳ)的相互作用.兰州大学学报(自然科学版),2004,40(2):62-66.
[120] 杨培慧,郑志雯,蔡继业.胆红素与血红蛋白分子作用的发光光谱分析.发光学报,2004,25(3):247-251.
[121] A. Sulkowska, J. Rownicka, B. Bojko, J. Pozycka, I. Zubik-Skupien, W. Sulkowski. Effect of guanidine hydrochloride on bovine serum albumin complex with antithyroid drugs: fluorescence study. Journal of Molecular Structure, 2004, 704(1-3): 291-295.
[122] H. Gao, L. Lei, J. Liu, Q. Kong, X. Chen, Z. Hu. The study on the interaction between human serum albumin and a new reagent with antitumour activity by spectrophotometric methods. Journal of Photochemistry and Photobiology A: Chemistry, 2004, 167(2-3): 213-221.
[123] 马贵斌,高飞,任斌知,杨频.荧光法研究药物分子与人血清白蛋白的结合作用.化学学报,1995,53(12):1193—1197.
[124] S. Bi, L. Ding, Y. Tian, D. Song, X. Zhou, X. Liu, H. Zhang. Investigation of the interaction between flavonoids and human serum albumin. Journal of Molecular Structure, 2004, 703(1-3): 37-45.
[125] E. L. Gelamo, M. Tabak. Spectroscopic studies on the interaction of bovine (BSA) and human (HSA) serum albumins with ionic surfactants. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2000, 56(11): 2255-2271.
[126] 白坚石,卜凤荣,李松,胡远东.聚乙二醇修饰牛血红蛋白制备红细胞代用品的初步研究.中国生物制品学杂志,2002,15(2):97-100.
[127] 梁宏,邢本刚,吴庆轩,罗济文,周永洽,中泮文.Cu(Ⅱ),Fe(Ⅲ)与人血清白蛋白相互作用的荧光光谱研究.化学学报,1999,57(2):161—165.
[128] A. Sulkowska. Interaction of drugs with bovine and human serum albumin. Journal of Molecular Structure, 2002, 614(1-3): 227-232.
[129] Q. Zhao, C. Le Coeur, J. M. Piot. Analysis of peptides from bovine hemoglobin and tuna myoglobin enzymatic hydrolysate: use of HPLC with on-line second-order derivative spectroscopy for the characterization of biologically active peptides. Analytica Chimica Acta, 1997, 352(1-3): 201-220.
[130] B. X. Huang, H. -Y. Kim, C. Dass. Probing three-dimensional structure of bovine serum albumin by chemical cross-linking and mass spectrometry. Journal of the American Society for Mass Spectrometry, 2004, 15(8): 1237-1247.
[131] W. L. Nichols, B. H. Zimm, L. F. Ten Eyck. Conformation-invariant structures of the α_1β_1human hemoglobin dimer. Journal of Molecular Biology, 1997, 270(4): 598-615.
[132] L. G. Sultatos, K. M. Basker, M. Shao, S. D. Murphy. The interaction of the phosphorothioate insecticides chlorpyrifos and parathion and their oxygen analogues with bovine serum albumin. Molecular Pharmacology, 1984, 26: 99-104.
[133] M. M. Khan, S. Muzammil, S. Tayyab. Role of salt bridge(s) in the binding and photoconversion of bilirubin bound to high affinity site on human serum albumin. Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular Enzymology, 2000, 1479(1-2): 103-113.
[134] 邱立红,张文吉.多功能氧化酶系(MFO)与棉铃虫抗约性关系初步研究.农药学学报,1999,1(2):54—60.
[135] 贺锡雯,张伟华,吕京,崔涛,谢广云.氰戊菊酯对细胞色素P450281/282的诱导.中国药理学与毒理学杂志,1999,13(3):222-226.
[136] 王青秀,吴纯启,廖明阳.细胞色素P450表达的诱导机制及其筛选方法的研究进展.国外医学约学分册,2003,30(1):43—46.
[137] J. A. Hasler, R. Estabrook, M. Murray, I. Pikuleva, M. Waterman, J. Capdevila, V. Holla, C. Helvig, J. R. Falck, G. Farrell, L. S. Kaminsky, S. D. Spivack, E. Boitier, P. Beaune. Human cytochromes P450. Molecular Aspects of Medicine, 1999, 20(1-2): 1-137.
[138] M. Paolini, R. Mesirca, L. Pozzetti, A. Sapone, G. Cantelli-Forti. Molecular non-genetic biomarkers related to Fenarimol cocarcinogenesis: organ- and sex-specific CYP induction in rat. Cancer Letters, 1996, 101(2): 171-178.
[139] 王文林.方差分析.见:李春喜,王文林,主编.生物统计学.北京:科学出版社,1997.p:84-90.
[140] G. Lemaire, G. de Sousa, R. Rahmani. A PXR reporter gene assay in a stable cell culture system: CYP3A4 and CYP2B6 induction by pesticides. Biochemical Pharmacology, 2004, 68(12): 2347-2358.
[141] C. Delescluse, N. Ledirac, G. de Sousa, M. Pralavorio, P. Lesca, R. Rahmani. Cytotoxic effects and induction of cytochromes P450 1A1/2 by insecticides, in hepatic or epidermal cells: binding capability to the Ah receptor. Toxicology Letters, 1998, 96-97: 33-39.
[142] F. M. Buratti, M.T. Volpe, L. Fabrizi, A. Meneguz, L. Vittozzi, E. Testai. Kinetic parameters of OPT pesticide desulfuration by c-DNA expressed human CYPs. Environmental Toxicology and Pharmacology, 2002, 11(3-4): 181-190.
[143] F. P. Guengerich, T. Shimada. Activation of procarcinogens by human cytochrome P450 enzymes. Mutation Research, 1998, 400(1-2): 201-213.
[144] S. Imaoka, M. Osada, Y. Minamiyama, T. Yukimura, S. Toyokuni, S. Takemura, T. Hiroi, Y. Funae. Role of phenobarbital-inducible cytochrome P450s as a source of active oxygen species in DNA-oxidation. Cancer Letters, 2004, 203(2): 117-125.
[145] V. Lundblad. DNA ends: maintenance of chromosome termini versus repair of double strand breaks. Mutation Research, 2000, 451(1-2): 227-240.
[146] 杨克敌,顾祖维.细胞损伤的分子机理,化学物的致突变作用.见:夏世钧,吴中亮,主编.分子毒理学基础.武汉:湖北科学技术出版社,2001.p:90,104.
[147] T. Godard, P. Gauduchon, C. Debout. A first step in visual identification of different cell populations by a modified alkaline comet assay. Mutation Research, 2002, 520(1-2): 207-211.
[148] 余卫,孙金苏,闫长会,张慧丽.体外硫芥对人外周血淋巴细胞DNA的损伤.癌变.畸变·突变,2001,13(1):17-19.
[149] D. Bagchi, M. Bagchi, E. A. Hassoun, S. J. Stohs. In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides. Toxicology, 1995, 104(1-3): 129-140.
[150] P. B. Farmer. DNA and protein adducts as markers of genotoxicity. Toxicology Letters, 2004, 149(1-3): 3-9.
[151] P. J. McHugh, V. J. Spanswick, J. A. Hartley. Repair of DNA interstrand crosslinks: molecular mechanisms and clinical relevance. Lancet Oncology, 2001, 2(8): 483-490.
[152] R. C. Gupta, G. Spencer-Beach. Natural and endogenous DNA adducts as detected by ~(32)p-postlabeling. Regulatory Toxicology and Pharmacology, 1996, 23(1): 14-21.
[153] M. Dhouib, A. Pfohl-Leszkowicz, G. Dirheimer, A. Lugnier. DNA adducts formation induced in rat by endosulfan. Toxicology Letters, 1995, 78(Supplement 1): 28-29.
[154] R. G. Shah, J. Lagueux, S. Kapur, P. Levallois, P. Ayotte, M. Tremblay, J. Zee, G. G. Poirier. Determination of genotoxicity of the metabolites of the pesticides Guthion, Sencor, Lorox, Reglone, Daconil and Admire by ~(32)P-postlabeling. Molecular and Cellular Biochemistry, 1997, 169: 177-184.
[155] 雷毅雄,庄志雄,张桥.外来化学物与DNA-蛋白质交联物关系的研究进展.国外医学卫生学分册,1995,22(3):149-153.
[156] Y. -C. Hong, K. -H. Lee. Enhancement of DNA damage and involvement of reactive oxygen species after exposure to bitumen with UVA irradiation. Mutation Research, 1999, 426(1): 63-69.
[157] S. K. Chakrabarti, C. Bai, K. S. Subramanian. DNA-protein crosslinks induced by nickel compounds in isolated rat renal cortical cells and its antagonism by specific amino acids and magnesium ion. Toxicology and Applied Pharmacology, 1999, 154(3): 245-255.
[158] Y. Lei, Q, Zhang, Z. Zhuang. Induction of DNA-protein crosslink in rat lung and blood cells by the carcinogen nickel. Lung Cancer, 1996, 14(Supplement 1): S244.
[159] F. -Y. Wu, Y. -J. Lee, D. -R. Chen, H. -W. Kuo. Association of DNA-protein crosslinks and breast cancer. Mutation Research, 2002, 501 (1-2): 69-78.
[160] S. D. Hester, G. B. Benavides, L. Yoon, K. T. Morgan, F. Zou, W. Barry, D. C. Wolf. Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium. Toxicology, 2003, 187(1): 13-24.
[161] 杨胜利,张巧,宋爱云,宫亚欧,张谭沐.冬凌草甲素对大鼠肺及肝原代细胞非程序DNA 合成的影响.河南医科大学学报,2001,36(4):415-416.
[162] S. K. Chakrabarti, C. Bai, K. S. Subramanian. DNA-protein crosslinks induced by nickel compounds in isolated rat lymphocytes: role of reactive oxygen species and specific amino acids. Toxicology and Applied Pharmacology, 2001, 170(3): 153-165.
[163] 李明炎,余龙江.生活方式对人群DNA加合物水平影响的研究.河北医学,2003,9(4):289-292.
[164] A. E. H. Newell, Y. M. N. Akkari, Y. Torimaru, A. Rosenthal, C. A. Reifsteck, B. Cox, M. Grompe, S. B. Olson. Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes. DNA Repair, 2004, 3(5): 535-542.
[165] D. E. Sawyer, D. B. Brown. Diminished decondensation and DNA synthesis in activated sperm from rats treated with cyclophosphamide. Toxicology Letters, 2000, 114(1-3): 19-26.
[166] N. P. Singh. Microgels for estimation of DNA strand breaks, DNA protein crosslinks and apoptosis. Mutation Research, 2000, 455(1-2): 111-127.
[167] 李寿祺,倪祖尧,宋晓鸥,刘玉清,刘晓蓉,赵林.有机磷农药诱变性的构效关系分析及分子机理.中国药理学与毒理学杂志,1993,7(2):93-99.
[168] F. Ruzicka, D. -S. ttuang, M. I. Donnelly, P. A. Frey. Methane monooxygenase catalyzed oxygenation of 1,1-dimethylcyclopropane: evidence for radical and carbocationic intermediates. Biochemistry, 1990, 29(7): 1696-1700.
[169] 崔金山,李海山,张淼,张玉敏,段志文.丙烯腈对DNA交联作用研究.中国工业医学杂志,2004,17(1):18-20.
[170] T. Shono, K. Ohsawa, J. E. Casida. Metabolism of trans- and cis-permethrin, trans- and cis-cypermethrin, and decamethrin by microsomal enzymes. Journal of Agricultural and Food Chemistry, 1979, 27(2): 316-325.
[171] R. F. Henderson. Species differences in the metabolism of olefins: implications for risk assessment. Chemico-Biological Interactions, 2001, 135-136: 53-64.
[172] 黄俊勇,冷欣夫.离体鼠肝细胞及P-450酶系与拟除虫菊酯类杀虫剂的相互作用.动物学报,1993,39(4):418—423.
[173] 石俊,张志.体内一体外试验检测不同组织中化学致癌物诱导的程序外DNA合成.癌变·畸变·突变,1995,7(2):69—74.
[174] W. M. Generoso, G. A. Sega, A. M. Lockhart, L. A. Hughes, K. T. Cain, N. L. A. Cacheiro, M. D. Shelby. Dominant lethal mutations, heritable translocations, and unscheduled DNA synthesis induced in male mouse germ cells by glycidamide, a metabolite of acrylamide. Mutation Research, 1996, 371(3-4): 175-183.
[175] 吕群,译.样品研究设计.见:戴维·布鲁西克(D.Brusick),原著.吕群,强义国,江绍慧,泽.赵寿元,校.遗传毒理学原理(Principles of Genetic Toxicology).上海:复旦大学出版社,1987.New York:Plenum Press,1980.p:218-221.
[176] V. Bianchi, E. Pontis, P. Richard. Changes of deoxyribonucleoside triphosphate pools induced by hydroxyurea and their relation to DNA synthesis. Journal of Biological Chemistry, 1986, 261: 16037-16042.
[177] S. -H. Ye, W. Zhou, J. Song, B. -C. Peng, D. Yuan, Y. -M. Lu, P. -P. Qi. Toxicity and health effects of vehicle emissions in Shanghai. Atmospheric Environment, 1999, 34(3): 419-429.
[178] J. Surralles, N. Xamena, A. Creus, R. Marcos. The suitability of the micronucleus assay in human lymphocytes as a new biomarker of excision repair. Mutation Research, 1995, 342(1-2): 43-59.
[179] 施正政,余应年.DNA甲基化与癌.实用肿瘤杂志,1990,5(4):247-249.
[180] 肖文华,刘为纹.DNA甲基化异常与肿瘤研究现状.肿瘤,1995,15(3):297-300.
[181] L. Tao, P. M. Kramer, R. Ge, M. A. Pereira. Effect of dichloroacetic acid and trichloroacetie acid on DNA methylation in liver and tumors of female B6C3F1 mice. Toxicological Sciences, 1998, 43(2): 139-144.
[182] R. Del Gaudio, R. Di Giaimo, G. Geraci. Genome methylation of the marine annelid worm Chaetopterus variopedatus: methylation of a CpG in an expressed HI histone gene. FEBS Letters, 1997, 417(1): 48-52.
[183] D. Chakrabarty, K. W. Yu, K. Y. paek. Detection of DNA methylation changes during somatic embryogenesis of Siberian ginseng (Eleuterococcus senticosus). Plant Science, 2003, 165(1): 61-68.
[184] M. Szyf. Targeting DNA methylation in cancer. Ageing Research Reviews, 2003, 2(3): 299-328.
[185] 曹树义,赵力军,汤乃军,王春华.氯乙烯诱变性研究.职业与健康,2005,21(3):447-448.
[186] 肖卫,王振全,李芝兰.丙烯腈雄性生殖毒性作用的调查与实验研究.中国公共卫生,2001,17(5):402-403.
[187] 江俊康,翁诗君.苯对雄性小鼠生殖系统的影响.中国工业医学杂志,2004,17(2):94—96.
[188] 王文祥,廖惠珍,曹建平,王章敬,林崴.亚慢性镉暴露对雄性大鼠生殖毒性的研究.中国公共卫生,2004,20(5):562-563.
[189] 金龙金,董杰影,张军明.小剂量氯化汞对小鼠的生殖毒性.环境与健康杂志,2004,21(2):75-77.
[190] 宣登峰,易建华,画伟.锰对小鼠精子的损害作用.工业卫生与职业病,2002,28(1):17-19.
[191] 朱心强,郑一凡,张群卫,姜槐,黄幸纾.硫丹对成年大鼠生精功能的影响和氧化损伤.中国约理学与毒理学杂志,2002,16(5):391-395.
[192] 谈立峰,孙雪照,李燕南,吉俊敏,王茜丽,陈龙生,卞倩,王守林.甲萘威农药生产职业暴露对男工精子和精液质量的影响.中华劳动卫生职业病杂志,2005,23(2):87—90.
[193] 李东阳,让蔚清,谢红卫,贺栋梁,龙鼎新.烹调油烟对雄性大鼠的生殖毒性.环境与健康杂志,2005,22(1):37-39.
[2] 敖聪聪.2003年世界销售过亿美元的农药品种.新农药,2005,(4):51-52.
[3] 束放,邵振润.2003年我国农药械市场概况与2004年农约械市场需求分析与展望.农约科学与管理,2004,25(2):34-36.
[4] 中华人民共和国农业部.中国农业信息网2003年数据资料,http://www.agri.gov.cn/sizl/2003/23.htm.
[5] C. Bolognesi, G. Morasso. Genotoxicity of pesticides: potential risk for consumers. Trends in Food Science & Technology, 2000, 11(5): 182-187.
[6] C. Bolognesi. Genotoxicity of pesticides: a review of human biomonitoring studies. Mutation Research, 2003, 543(3): 251-272.
[7] 张大宝.遗传毒性与疾病.见:印木泉,主编.遗传毒理学.北京:科学出版社,2002.p:353-356.
[8] M. Schneider, G. B. Quistad, J. E. Casida. Glutathione activation of chloropicrin in the Salmonella mutagenicity test. Mutation Research, 1999, 439(2): 233-238.
[9] J. Blasiak, P. Jaloszynski, A. Trzeciak, K. Szyfter. In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues. Mutation Research, 1999, 445(2): 275-283.
[10] 孙运光.有机磷农药的遗传毒性研究.国外医学卫生学分册,2000,27(6):349-352.
[11] 谈伟君,王心如,徐锡坤.八氯二丙醚对DNA交联作用的研究.铁道医学,1999,27(6):386-387.
[12] 刘贤德,程伟.除草剂精克草能对黄鳝的遗传毒性及二种物质的抑制作用.徐州师范大学学报(自然科学版),2000,18(2):56-58.
[13] J. Blasiak, D. Stan kowska. Genotoxicity of Malaoxon: Induction of oxidized and methylated bases and protective effect of α-tocopherol. Pesticide Biochemistry and Physiology, 2001, 71(2): 88-96.
[14] L. -E. Okoumassoun, D. Averill-Bates, M. Marion, F. Denizeau. Possible mechanisms underlying the mitogenic action of heptachlor in rat hepatocytes. Toxicology and Applied Pharmacology, 2003, 193(3): 356—369.
[15] T. J. Schrader, B. G. Boyes, T. I. Matula, C. Heroux-Metcalf, I. Langlois, R. H. Downie. In vitro investigation of toxaphene genotoxicity in S. typhimurium and Chinese hamster V79 lung fibroblasts. Mutation Research, 1998, 413(2): 159-168.
[16] C. H. Sierra-Torres, N. Cajas-Salazar, L. S. Hoyos, M. Zuleta, E. B. Whorton, W. W. Au. In vitro and in vivo genotoxic activity of miral, an organophosphorus insecticide used in Colombia. Mutation Research, 1998, 415(1): 59-67.
[17] M. J. Ruiz, D. Marzin. Genotoxicity of six pesticides by Salmonella mutagenicity test and SOS chromotest. Mutation Research, 1997, 390(3): 245-255.
[18] P. Das, G. John. Induction of sister chromatid exchanges and chromosome aberrations in vivo in Etroplus suratensis (Bloch) following exposure to organophosphorus pesticides. Toxicology Letters, 1999, 104(2): 111-116.
[19] C. Vigreux, J. M. Poul, E. Deslandes, P. Lebailly, T. Godard, F. Sichel, M. Henry-Amar, P. Gauduchon. DNA damaging effects of pesticides measured by the single cell gel electrophoresis assay (comet assay) and the chromosomal aberration test, in CHOK1 cells. Mutation Research, 1998, 419(2): 79-90.
[20] M. B. Lioi, M. R. Scarfi, A. Santoro, R. Barbieri, O. Zeni, D. Di Berardino, M. V. Ursini. Genotoxicity and oxidative stress induced by pesticide exposure in bovine lymphocyte cultures in vitro. Mutation Research, 1998, 403(1): 13-20.
[21] 谢志浩,蔡亚非,陈国,黄剑锋,余红卫.利用泥鳅红细胞微核及核异常测定法对四种除草剂遗传毒性的研究.现代农约,2002,(4):24-27.
[22] 耿德贵,张大生,程伟,陈刚,温洪宇.四种除草剂对中华大蟾蜍蝌蚪红细胞微核及核异常的影响.动物学杂志,2000,35(1):12-16.
[23] J. Surralles, N. Xamena, A. Creus, R. Marcos. Conversion of DNA adducts induced by pesticides and model mutagens to micronuclei in human lymphocytrs as new biomarker of excision repair. Mutation Research, 1995, 335(1): 77-78.
[24] A. Laouedj, C. Cschenk, A. Pfohl-leszkowicz, G. Keith, D. Schontz, P. Guillernaut, B. Dether. Detection of DNA adducts in declining hop plants grown on fields formerly treated with heptachlor, a persistent insecticide. Environmental Pollution, 1995, 90(3): 409-414.
[25] 石进元,王海芳,吴小红,李新松,刘元方,李坤,鲁向阳,汪建军,刘克新.用加速器质谱法研究低剂量抗蚜威的基因毒性.科学通报,1997,42(15):1675-1677.
[26] M. F. Rahman, M. Mahboob, K. Danadevi, B. S. Banu, P. Grover. Assessment of genotoxic effects of chloropyriphos and acephate by the comet assay in mice leucocytes. Mutation Research, 2002, 516(2): 139-147.
[27] S. Soloneski, M. Gonzalez, E. Piaggio, M.A. Reigosa, M. L. Larramendy. Effect of dithiocarbamate pesticide zineb and its commercial formulation, azzurro Ⅲ. Genotoxic evaluation on Chinese hamster ovary (CHO) cells. Mutation Research, 2002, 514(2): 201-212.
[28] 许丹倩.毒死蜱及其中间体的合成述评.浙江化工,1995,26(1):4-8.
[29] 中华人民共利国农业部农药检定所.中国农约信息网数据中心,http://www.chinapesticide.gov.cn/sjzx/yxcf.htm.
[30] J. L. Schardein, A. R. Scialli. The legislation of toxicologic safety factors: the food quality protection act with chlorpyrifos as a test case. Reproductive Toxicology, 1999, 13(1): 1-14.
[31] J. O. Lalah, D. Ondieki, S. O. Wandiga, I. O. Jumba. Dissipation, distribution, and uptake of ~(14)c-chlorpyrifos in a model tropical seawater/sediment/fish ecosystem. Bulletin of Environmental Contamination and Toxicology, 2003, 70: 883-890.
[32] R. C. Cochran. Appraisal of risks from nonoccupational exposure to chlorpyrifos. Regulatory Toxicology and Pharmacology, 2002, 35 (1): 105-121.
[33] 林郁,主编.农约应用大全.北京:农业出版社,1989.p:187,237.
[34] 吴慧明,魏方林,楼建晴,朱国念.毒死蜱的水解研究.宁波高等专科学校学报.2001,13(Sup):101-104.
[35] B. Liu, L. L. McConnell, A. Torrents. Hydrolysis of chlorpyrifos in natural waters of the Chesapeake Bay. Chemosphere, 2001, 44(6): 1315-1323.
[36] 唐除痴.杀虫剂及其他动物害物防治剂.见:唐除痴,李煜昶,陈彬,杨华铮,金桂玉,合编.农药化学.天津:南开大学出版社,1998.p:79,211.
[37] 岳永德,汤锋,花日茂,关伟,涂永志.混合农约及表面活性剂对毒死蜱光解影响的研究.安徽农业大学学报,2000,27(1):1-4.
[38] 吴慧明,朱国念.毒死蜱在灭菌和未灭菌土壤中的降解研究.农药学学报,2003,5(4):65-69.
[39] 施海萍,陈謇,叶建人.毒死蜱、乐果在大棚和露地青菜上的降解动态.浙江农业科学, 2002,(4):191-192.
[40] 范志金,刘丰茂,钱传范.氯氰菊酯的名称和组成及其光学异构体.农约科学与管理,1999,20(2):9-11,17.
[41] 俞明兴.新法合成氯氰菊酯的研究.安徽大学学报(自然科学版),1992,16(4):69-72.
[42] T. J. Smith, D. M. Soderlund. Potent actions of the pyrethroid insecticides cismethrin and cypermethrin on rat tetrodotoxin-resistant peripheral nerve (SNS/PN3) sodium channels expressed in Xenopus oocytes. Pesticide Biochemistry and Physiology, 2001, 70(1): 52-61.
[43] 夏会龙,陈宗懋.氯氰菊酯和马拉硫磷农约的水解动力学研究.农业环境保护,1989,8(5):1-3.
[44] 花日茂,岳永德,汤锋,李学德,樊德方.4种农约对3种拟菊酯杀虫剂在不同光源下的光解效应.中国环境科学,1997,17(1):72-75.
[45] 秦曙,乔雄梧,朱九生,王静.实验室条件下氯氰菊酯在土壤中的降解.农药学学报,2000,2(3):68-73.
[46] 商博,王洪涛,彭全民.三种农药在不同作物上残留动态的研究.农药,1990,29(3):31-32.
[47] 孙建析,沈芸芝,乐俊仪,杨校华.毒死蜱大鼠亚慢性毒性试验.浙江省医学科学院学报,1998,9(1):11-13.
[48] A. Goel, V. Dani, D. K. Dhawan. Protective effects of zinc on lipid peroxidation, antioxidant enzymes and hepatic: histoarchitecture in chlorpyrifos-induced toxicity. Chemico-Biological Interactions, 2005, 156(2-3): 131-140.
[49] J. T. Auman, F. J. Seidler, T. A. Slotkin. Neonatal chlorpyrifos exposure targets multiple proteins governing the hepatic adenylyl cyclase signaling cascade: implications for neurotoxicity. Developmental Brain Research, 2000, 121 (1): 19-27.
[50] R. A. Schuh, P. J. Lein, R. A. Beckles, D. A. Jett. Noncholinesterase mechanisms of chlorpyrifos neurotoxicity: altered phosphorylation of Ca~(2+)/cAMP response element binding protein in cultured neurons. Toxicology and Applied Pharmacology, 2002, 182(2): 176-185.
[51] J. A. Bomser, G. B. Quistad, J. E. Casida. Chlorpyrifos oxon potentiates diacylglycerol-induced extracellular signal-regulated kinase (ERK 44/42) activation, possibly by diacylglycerol lipase inhibition. Toxicology and Applied Pharmacology, 2002, 178(1): 29-36.
[52] M. Ghisari, E. C. Bonefeld-Jorgensen. Impact of environmental chemicals on the thyroid hormone function in pituitary rat GH3 cells. Molecular and Cellular Endocrinology, 2005, 244(1): 31-41.
[53] H.R. Andersen, A.M. Vinggaard, T.H. Rasmussen, I.M. Gjermandsen, E.C. Bonefeld-Jorgensen. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Toxicology and Applied Pharmacology, 2002, 179(1): 1-12.
[54] H.T. Grunfeld, E.C. Bonefeld-Jorgensen. Effect of in vitro estrogenic pesticides on human oestrogen receptor a and ft mRNA levels. Toxicology Letters, 2004, 151(3): 467-480
[55] A.T. Farag, A.M. El Okazy, A.F. El-Aswed. Developmental toxicity study of chlorpyrifos in rats. Reproductive Toxicology, 2003, 17(2): 203-208.
[56] Y. Tian, H. Ishikawa, T. Yamaguchi, T. Yamauchi, K. Yokoyama. Teratogenicity and developmental toxicity of chlorpyrifos: maternal exposure during organogenesis in mice. Reproductive Toxicology, 2005, 20(2): 267-271.
[57] H.A. Navarro, P.V. Basta, F.J. Seidler, T.A. Slotkin. Neonatal chlorpyrifos administration elicits deficits in immune function in adulthood: a neural effect? Developmental Brain Research, 2001, 130(2): 249-252.
[58] K.P. Das, S. Barone Jr. Neuronal differentiation in PC12 cells is inhibited by chlorpyrifos and its metabolites: is acetylcholinesterase inhibition the site of action? Toxicology and Applied Pharmacology, 1999, 160(3): 217-230.
[59] A.S. Howard, R. Bucelli, D.A. Jett, D. Bruun, D. Yang, P.J. Lein. Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures. Toxicology and AppliedPharmacology, 2005, 207(2): 112-124.
[60] M.-G. Zurich, P. Honegger, B. Schilter, L.G. Costa, F. Monnet-Tschudi. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos. Toxicology and Applied Pharmacology, 2004, 201 (2): 97-104.
[61] S.J. Garcia, F.J. Seidler, D. Qiao, T.A. Slotkin. Chlorpyrifos targets developing glia: effects on glial fibrillary acidic protein. Developmental Brain Research, 2002, 133(2): 151-161.
[62] M. Guizzetti, S. Pathak, G. Giordano, L.G. Costa. Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation. Toxicology, 2005, 215(3): 182-190.
[63] T.A. Slotkin, F.J. Seidler. The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent. Developmental Brain Research, 2005, 158(1-2): 115-119.
[64] K..W. Raines, F.J. Seidler, T.A. Slotkin. Alterations in serotonin transporter expression in brain regions of rats exposed neonatally to chlorpyrifos. Developmental Brain Research, 2001, 130(1): 65-72.
[65] T. A. Slotkin, C. A. Tate, M. M. Cousins, F. J. Seidler. Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure. Developmental Brain Research, 2002, 133(2): 163-173.
[66] K. Dam, F. J. Seidler, T. A. Slotkin. Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration. Developmental Brain Research, 1998, 108(1-2): 39-45.
[67] T. L. Crumpton, F. J. Seidler, T. A. Slotkin. Developmental neurotoxicity of chlorpyrifos in vivo and in vitro: effects on nuclear transcription factors involved in cell replication and differentiation. Brain Research, 2000, 857(1-2): 87-98.
[68] K. Dam, F. J. Seidler, T. A. Slotkin. Transcriptional biomarkers distinguish between vulnerable periods for developmental neurotoxicity of chlorpyrifos: implications for toxicogenomics. Brain Research Bulletin, 2003, 59(4): 261-265.
[69] T. L. Crumpton, F. J. Seidler, T. A. Slotkin. Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos? Developmental Brain Research, 2000, 121(2): 189-195.
[70] D. K. Parran, G. Magnin, W. Li, B. S. Jortner, M. Ehrich. Chlorpyrifos alters functional integrity and structure of an in vitro BBB model: co-cultures of bovine endothelial cells and neonatal rat astrocytes. Neuro Toxicology, 2005, 26(1): 77-88.
[71] K. Dam, F. J. Seidler, T. A. Slotkin. Chlorpyrifos releases norepinephrine from adult and neonatal rat brain synaptosomes. Developmental Brain Research, 1999, 118(1-2): 129-133.
[72] J. R. Bloomquist, R. L. Barlow, J. S. Gillette, W. Li, M. L. Kirby. Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways. Neuro Toxicology, 2002, 23(4-5): 537-544.
[73] C. J. Gordon, B. K. Padnos. Prolonged elevation in blood pressure in the unrestrained rat exposed to chlorpyrifos. Toxicology, 2000, 146(1): 1-13.
[74] 李寿祺,刘玉清,倪祖尧,宋晓鸥,刘晓蓉,赵林.24种有机磷农药的诱变性.中国药理学与毒理学杂志,1993,7(1):73-77.
[75] B. B. Gollapudi, A. L. Mendrala, V. A. Linscombe. Evaluation of the genetic toxicity of the organophosphate insecticide chlorpyrifos. Mutation Research, 1995, 342(1-2): 25-36.
[76] 宋晓鸥,林凡,姜幼纯,刘晓蓉,张培厚,刘玉清.19种有机磷农约对酵母D61.M菌株的 诱变性.中国药理学与毒理学杂志,1997,11(4):291-293.
[77] Y. Tian, T. Yamauchi. Micronucleus formation in 3-day mouse embryos associated with maternal exposure to chlorpyrifos during the early preimplantation period. Reproductive Toxicology, 2003, 17(4): 401-405.
[78] B. Dimitrov, P. Gadeva. Genotoxicity studies on the insecticide dursban in root meristem cells of Crepis capillaris L.. Environmental and Experimental Botany, 1997, 37(2-3): 199-209.
[79] 刘永霞,张树来,史岩,谢琳.农药氯氰菊酯的毒性实验.职业与健康,2003,19(6):37-38.
[80] B. Giray, A. Gürbay, F. Hincal. Cypermethrin-induced oxidative stress in rat brain and liver is prevented by Vitamin E or allopurinol. Toxicology Letters, 2001, 118(3): 139-146.
[81] M. Kale, N. Rathore, S. John, D. Bhatnagar. Lipid peroxidative damage on pyrethroid exposure and alterations in antioxidant status in rat erythrocytes: a possible involvement of reactive oxygen species. Toxicology Letters, 1999, 105(3): 197-205.
[82] R. Gabbianelli, G. Falcioni, C. Nasuti, F. Cantalamessa. Cypermethrin-induced plasma membrane perturbation on erythrocytes from rats: reduction of fluidity in the hydrophobic core and in glutathione peroxidase activity. Toxicology, 2002, 175(1-3): 91-101.
[83] P. Grajeda-Cota, M. V. Ramirez-Mares, E. G. de Mejia. Vitamin C protects against in vitro cytotoxicity of cypermethrin in rat hepatocytes. Toxicology in Vitro, 2004, 18(1): 13-19.
[84] L. Aldana, E. G. de Mejia, A. Craigmill, V. Tsutsumi, J. Armendariz-Borunda, A. Panduro, A. R. Rincon. Cypermethrin increases apo A-1 and apo B mRNA but not hyperlipidemia in rats. Toxicology Letters, 1998, 95(1): 31-39.
[85] 夹访贤,张秀莲,于丽华.氯氰菊酯对大鼠肝线粒体、微粒体钙离子转运的影响.中国公共卫生学报,1994,13(5):257-259.
[86] 张秀莲,夹访贤,于丽华.拟除虫菊酯类农约对大鼠肝线粒体、微粒体Ca(2+)-ATP酶活力的影响.中国公共卫生学报,1994,13(5):303-305.
[87] 夹访贤,张秀莲,于丽华.氯氰菊酯对大鼠肝脏磷酸化酶a、Ca~(2+)-ATP酶活力的影响.中国公共卫生学报,1995,14(2):88-89.
[88] 张秀莲,夹访贤,于丽华,菅向东,王海石.除虫菊酯类农药对大鼠肝线粒体、微粒体~(45)Ca摄取的影响.中华劳动卫生职业病杂志,1997,15(5):258-260.
[89] G. de Sousa, F. Fontaine, M. Pralavorio, D. Botta-Fridlund, Y. Letreut, R. Rahmani. Insecticide cytotoxicity and CYP1A1/2 induction in primary human and rat hepatocyte cultures. Toxicology in Vitro, 1997, 11(5): 451—457.
[90] A. F. Heder, K. I. Hirsch-Ernst, D. Bauer, G. F. Kahl, H. Desel. Induction of cytochrome P450 2B1 by pyrethroids in primary rat hepatocyte cultures. Biochemical Pharmacology, 2001, 62(1): 71-79.
[91] K. S. El-Gendy, N. M. Aly, E. Rashwaan, A. H. El-Sebae. Biochemical targets affected by sublethal doses of cypermethrin. Toxicology Letters, 1998, 95 (Supplement 1): 143.
[92] L. Instit6ris, O. Siroki, U. Undeger, I. Desi, L. Nagymajtenyi. Immunotoxicological effects of repeated combined exposure by cypermethrin and the heavy metals lead and cadmium in rats. International Journal of lmmunopharmacology, 1999, 21(11): 735-743.
[93] L. Institoris, U. Undeger, O. Siroki, M. Nehez, I. Desi. Comparison of detection sensitivity of immuno- and genotoxicological effects of subacute cypermethrin and permethrin exposure in rats. Toxicology. 1999, 137(1): 47-55.
[94] 童建,朱本兴,王道锦.氯氰菊酯对淋巴细胞信使昼夜节律的影响.卫生毒理学杂志,1997,11(3):144-147.
[95] 陈海热,王心如,肖继皋,胡刚,宋玲,王守林,何凤生.有机磷与拟除虫菊酯农药的拟雌激素活性研究.中华劳动卫生职业病杂志,2001,19(4):274-277.
[96] G. Santoni, F. Cantalamessa, L. Mazzucca, S. Romagnoli, M. Piccoli. Prenatal exposure to cypermethrin modulates rat NK cell cytotoxic functions. Toxicology, 1997, 120(3): 231-242.
[97] G. Santoni, F. Cantalamessa, R. Cavagna, S. Romagnoli, E. Spreghini, M. Piccoli. Cypermethrin-induced alteration of thymocyte distribution and functions in prenatally-exposed rats. Toxicology, 1998, 125(1): 67-78.
[98] F. Cantalamessa, P. Barili, R. Cavagna, M. Sabbatini, G. Tenore, F. Amenta. Influence of neonatal treatment with the pyrethroid insecticide cypermethrin on the development of dopamine receptors in the rat kidney. Mechanisms of Ageing and Development, 1998, 103(2): 165-178.
[99] A. Gupta, A. K. Agarwal, G. S. Shukla. Effect of quinalphos and cypermethrin exposure on developing blood-brain barrier: role of nitric oxide. Environmental Toxicology and Pharmacology, 2000, 8(2): 73-78.
[100] 1. Kakko, T. Toimela, H. Tahti. The toxicity of pyrethroid compounds in neural cell cultures studied with total ATP, mitochondrial enzyme activity and microscopic photographing. Environmental Toxicology and Pharmacology, 2004, 15(2-3): 95-102.
[101] I. Kakko, T. Toimela, H. Tahti. The synaptosomal membrane bound ATPase as a target for the neurotoxic effects of pyrethroids, permethrin and cypermethrin. Chemosphere, 2003, 51(6): 475-480.
[102] G. V. Rao, K. S. J. Rao. Modulation of K~+ transport across synaptosomes of rat brain by synthetic pyrethroids. Journal of the Neurological Sciences, 1997, 147(2): 127-133.
[103] 吴建平,夏若寒,石年,刘毓谷.拟除虫菊酯对大鼠脑突触体谷氨酸摄取功能的影响.卫生研究,1999,28(5):261-262.
[104] 吴建平,卢春,干英,祝卫国,夏若寒,石年,刘毓谷.拟除虫菊酯对大鼠中枢谷氨酸和γ-氨基丁酸递质影响的免疫组织化学研究.南京医科大学学报,1999,19(6):450-453.
[105] 吴建平,夏若寒,石年,刘毓谷.氯氰菊酯诱导大鼠中枢一氧化氮合酶表达增强.南京医科大学学报,1999,19(5):357-359.
[106] M. Condes-Lara, A. Graff-Guerrero, L. Vega-Riveroll. Effects of cyperrnethrin on the electroencephalographic activity of the rat: a model of chemically induced seizures. Neurotoxicology and Teratology, 1999, 21(3): 293-298.
[107] L. K. S. Chauhan, P. N. Saxena, S. K. Gupta. Cytogenetic effects of cypermethrin and fenvalerate on the root meristem cells of Allium cepa. Environmental and Experimental Botany, 1999, 42(3): 181-189.
[108] J. Surralles, N. Xamena, A. Creus, J. Catalan, H. Norppa, R. Marcos. Induction of micronuclei by five pyrethroid insecticides in whole blood and isolated human lymphocyte cultures. Mutation Research, 1995, 341 (3): 169-184.
[109] 陆肇红,童建,朱金华.氯氰菊酯微核率的时间效应.苏州医学院学报,1995,15(5):836—837.
[110] L. K. S. Chauhan, D. K. Agarwal, V. Sundararaman. In vivo induction of sister chromatid exchange in mouse bone marrow following oral exposure to commercial formulations of alpha-cyano pyrethroids. Toxicology Letters, 1997, 93(2-3): 153-157.
[111] Y. Shukla, A. Yadav, A,. Arora. Carcinogenic and cocarcinogenic potential of cypermethrin on mouse skin. Cancer Letters, 2002, 182(1): 33-41.
[112] S. F. Donovan, M. C. Pescatore. Method for measuring the logarithm of the octanol-water partition coefficient by using short octadecyl-poly(vinyl alcohol) high-performance liquid chromatography columns. Journal of Chromatography A, 2002, 952(1-2): 47-61.
[113] 马贵斌,杨频.荧光法研究维生素B_6和芦丁与白蛋白的相互作用.生物化学与生物物理进展,1990,17(4):290-295.
[114] D. Silva, C. M. Cortez, J. Cunha-Bastos, S. R. W. Louro. Methyl parathion interaction with human and bovine serum albumin. Toxicology Letters, 2004, 147(1): 53-61.
[115] 杨斌盛,杨频.人血清白蛋白与金属离子作用的荧光光谱研究.生物化学与生物物理进展,1992,19(2):110-114.
[116] R. Jaiswal, M. A. Khan, J. Musarrat. Photosensitized paraquat-induced structural alterations and free radical mediated fragmentation of serum albumin. Journal of Photochemistry and Photobiology B: Biology, 2002, 67(3): 163-170.
[117] 查冠林.细胞毒理学血细胞学基础.见:刘国廉,主编.细胞毒理学.北京:军事医学科学出版社,2001.p:236-269.
[118] 黄淑萍,陈亮,李玉红.比较与研究金属离子与三种蛋白的配位机理.光谱学与光谱分析,1995,15(5):85-89.
[119] 常希俊,杨芳,张莉,王邃.牛血红蛋白与镝(Ⅲ)、钛(Ⅳ)的相互作用.兰州大学学报(自然科学版),2004,40(2):62-66.
[120] 杨培慧,郑志雯,蔡继业.胆红素与血红蛋白分子作用的发光光谱分析.发光学报,2004,25(3):247-251.
[121] A. Sulkowska, J. Rownicka, B. Bojko, J. Pozycka, I. Zubik-Skupien, W. Sulkowski. Effect of guanidine hydrochloride on bovine serum albumin complex with antithyroid drugs: fluorescence study. Journal of Molecular Structure, 2004, 704(1-3): 291-295.
[122] H. Gao, L. Lei, J. Liu, Q. Kong, X. Chen, Z. Hu. The study on the interaction between human serum albumin and a new reagent with antitumour activity by spectrophotometric methods. Journal of Photochemistry and Photobiology A: Chemistry, 2004, 167(2-3): 213-221.
[123] 马贵斌,高飞,任斌知,杨频.荧光法研究药物分子与人血清白蛋白的结合作用.化学学报,1995,53(12):1193—1197.
[124] S. Bi, L. Ding, Y. Tian, D. Song, X. Zhou, X. Liu, H. Zhang. Investigation of the interaction between flavonoids and human serum albumin. Journal of Molecular Structure, 2004, 703(1-3): 37-45.
[125] E. L. Gelamo, M. Tabak. Spectroscopic studies on the interaction of bovine (BSA) and human (HSA) serum albumins with ionic surfactants. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2000, 56(11): 2255-2271.
[126] 白坚石,卜凤荣,李松,胡远东.聚乙二醇修饰牛血红蛋白制备红细胞代用品的初步研究.中国生物制品学杂志,2002,15(2):97-100.
[127] 梁宏,邢本刚,吴庆轩,罗济文,周永洽,中泮文.Cu(Ⅱ),Fe(Ⅲ)与人血清白蛋白相互作用的荧光光谱研究.化学学报,1999,57(2):161—165.
[128] A. Sulkowska. Interaction of drugs with bovine and human serum albumin. Journal of Molecular Structure, 2002, 614(1-3): 227-232.
[129] Q. Zhao, C. Le Coeur, J. M. Piot. Analysis of peptides from bovine hemoglobin and tuna myoglobin enzymatic hydrolysate: use of HPLC with on-line second-order derivative spectroscopy for the characterization of biologically active peptides. Analytica Chimica Acta, 1997, 352(1-3): 201-220.
[130] B. X. Huang, H. -Y. Kim, C. Dass. Probing three-dimensional structure of bovine serum albumin by chemical cross-linking and mass spectrometry. Journal of the American Society for Mass Spectrometry, 2004, 15(8): 1237-1247.
[131] W. L. Nichols, B. H. Zimm, L. F. Ten Eyck. Conformation-invariant structures of the α_1β_1human hemoglobin dimer. Journal of Molecular Biology, 1997, 270(4): 598-615.
[132] L. G. Sultatos, K. M. Basker, M. Shao, S. D. Murphy. The interaction of the phosphorothioate insecticides chlorpyrifos and parathion and their oxygen analogues with bovine serum albumin. Molecular Pharmacology, 1984, 26: 99-104.
[133] M. M. Khan, S. Muzammil, S. Tayyab. Role of salt bridge(s) in the binding and photoconversion of bilirubin bound to high affinity site on human serum albumin. Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular Enzymology, 2000, 1479(1-2): 103-113.
[134] 邱立红,张文吉.多功能氧化酶系(MFO)与棉铃虫抗约性关系初步研究.农药学学报,1999,1(2):54—60.
[135] 贺锡雯,张伟华,吕京,崔涛,谢广云.氰戊菊酯对细胞色素P450281/282的诱导.中国药理学与毒理学杂志,1999,13(3):222-226.
[136] 王青秀,吴纯启,廖明阳.细胞色素P450表达的诱导机制及其筛选方法的研究进展.国外医学约学分册,2003,30(1):43—46.
[137] J. A. Hasler, R. Estabrook, M. Murray, I. Pikuleva, M. Waterman, J. Capdevila, V. Holla, C. Helvig, J. R. Falck, G. Farrell, L. S. Kaminsky, S. D. Spivack, E. Boitier, P. Beaune. Human cytochromes P450. Molecular Aspects of Medicine, 1999, 20(1-2): 1-137.
[138] M. Paolini, R. Mesirca, L. Pozzetti, A. Sapone, G. Cantelli-Forti. Molecular non-genetic biomarkers related to Fenarimol cocarcinogenesis: organ- and sex-specific CYP induction in rat. Cancer Letters, 1996, 101(2): 171-178.
[139] 王文林.方差分析.见:李春喜,王文林,主编.生物统计学.北京:科学出版社,1997.p:84-90.
[140] G. Lemaire, G. de Sousa, R. Rahmani. A PXR reporter gene assay in a stable cell culture system: CYP3A4 and CYP2B6 induction by pesticides. Biochemical Pharmacology, 2004, 68(12): 2347-2358.
[141] C. Delescluse, N. Ledirac, G. de Sousa, M. Pralavorio, P. Lesca, R. Rahmani. Cytotoxic effects and induction of cytochromes P450 1A1/2 by insecticides, in hepatic or epidermal cells: binding capability to the Ah receptor. Toxicology Letters, 1998, 96-97: 33-39.
[142] F. M. Buratti, M.T. Volpe, L. Fabrizi, A. Meneguz, L. Vittozzi, E. Testai. Kinetic parameters of OPT pesticide desulfuration by c-DNA expressed human CYPs. Environmental Toxicology and Pharmacology, 2002, 11(3-4): 181-190.
[143] F. P. Guengerich, T. Shimada. Activation of procarcinogens by human cytochrome P450 enzymes. Mutation Research, 1998, 400(1-2): 201-213.
[144] S. Imaoka, M. Osada, Y. Minamiyama, T. Yukimura, S. Toyokuni, S. Takemura, T. Hiroi, Y. Funae. Role of phenobarbital-inducible cytochrome P450s as a source of active oxygen species in DNA-oxidation. Cancer Letters, 2004, 203(2): 117-125.
[145] V. Lundblad. DNA ends: maintenance of chromosome termini versus repair of double strand breaks. Mutation Research, 2000, 451(1-2): 227-240.
[146] 杨克敌,顾祖维.细胞损伤的分子机理,化学物的致突变作用.见:夏世钧,吴中亮,主编.分子毒理学基础.武汉:湖北科学技术出版社,2001.p:90,104.
[147] T. Godard, P. Gauduchon, C. Debout. A first step in visual identification of different cell populations by a modified alkaline comet assay. Mutation Research, 2002, 520(1-2): 207-211.
[148] 余卫,孙金苏,闫长会,张慧丽.体外硫芥对人外周血淋巴细胞DNA的损伤.癌变.畸变·突变,2001,13(1):17-19.
[149] D. Bagchi, M. Bagchi, E. A. Hassoun, S. J. Stohs. In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides. Toxicology, 1995, 104(1-3): 129-140.
[150] P. B. Farmer. DNA and protein adducts as markers of genotoxicity. Toxicology Letters, 2004, 149(1-3): 3-9.
[151] P. J. McHugh, V. J. Spanswick, J. A. Hartley. Repair of DNA interstrand crosslinks: molecular mechanisms and clinical relevance. Lancet Oncology, 2001, 2(8): 483-490.
[152] R. C. Gupta, G. Spencer-Beach. Natural and endogenous DNA adducts as detected by ~(32)p-postlabeling. Regulatory Toxicology and Pharmacology, 1996, 23(1): 14-21.
[153] M. Dhouib, A. Pfohl-Leszkowicz, G. Dirheimer, A. Lugnier. DNA adducts formation induced in rat by endosulfan. Toxicology Letters, 1995, 78(Supplement 1): 28-29.
[154] R. G. Shah, J. Lagueux, S. Kapur, P. Levallois, P. Ayotte, M. Tremblay, J. Zee, G. G. Poirier. Determination of genotoxicity of the metabolites of the pesticides Guthion, Sencor, Lorox, Reglone, Daconil and Admire by ~(32)P-postlabeling. Molecular and Cellular Biochemistry, 1997, 169: 177-184.
[155] 雷毅雄,庄志雄,张桥.外来化学物与DNA-蛋白质交联物关系的研究进展.国外医学卫生学分册,1995,22(3):149-153.
[156] Y. -C. Hong, K. -H. Lee. Enhancement of DNA damage and involvement of reactive oxygen species after exposure to bitumen with UVA irradiation. Mutation Research, 1999, 426(1): 63-69.
[157] S. K. Chakrabarti, C. Bai, K. S. Subramanian. DNA-protein crosslinks induced by nickel compounds in isolated rat renal cortical cells and its antagonism by specific amino acids and magnesium ion. Toxicology and Applied Pharmacology, 1999, 154(3): 245-255.
[158] Y. Lei, Q, Zhang, Z. Zhuang. Induction of DNA-protein crosslink in rat lung and blood cells by the carcinogen nickel. Lung Cancer, 1996, 14(Supplement 1): S244.
[159] F. -Y. Wu, Y. -J. Lee, D. -R. Chen, H. -W. Kuo. Association of DNA-protein crosslinks and breast cancer. Mutation Research, 2002, 501 (1-2): 69-78.
[160] S. D. Hester, G. B. Benavides, L. Yoon, K. T. Morgan, F. Zou, W. Barry, D. C. Wolf. Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium. Toxicology, 2003, 187(1): 13-24.
[161] 杨胜利,张巧,宋爱云,宫亚欧,张谭沐.冬凌草甲素对大鼠肺及肝原代细胞非程序DNA 合成的影响.河南医科大学学报,2001,36(4):415-416.
[162] S. K. Chakrabarti, C. Bai, K. S. Subramanian. DNA-protein crosslinks induced by nickel compounds in isolated rat lymphocytes: role of reactive oxygen species and specific amino acids. Toxicology and Applied Pharmacology, 2001, 170(3): 153-165.
[163] 李明炎,余龙江.生活方式对人群DNA加合物水平影响的研究.河北医学,2003,9(4):289-292.
[164] A. E. H. Newell, Y. M. N. Akkari, Y. Torimaru, A. Rosenthal, C. A. Reifsteck, B. Cox, M. Grompe, S. B. Olson. Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes. DNA Repair, 2004, 3(5): 535-542.
[165] D. E. Sawyer, D. B. Brown. Diminished decondensation and DNA synthesis in activated sperm from rats treated with cyclophosphamide. Toxicology Letters, 2000, 114(1-3): 19-26.
[166] N. P. Singh. Microgels for estimation of DNA strand breaks, DNA protein crosslinks and apoptosis. Mutation Research, 2000, 455(1-2): 111-127.
[167] 李寿祺,倪祖尧,宋晓鸥,刘玉清,刘晓蓉,赵林.有机磷农药诱变性的构效关系分析及分子机理.中国药理学与毒理学杂志,1993,7(2):93-99.
[168] F. Ruzicka, D. -S. ttuang, M. I. Donnelly, P. A. Frey. Methane monooxygenase catalyzed oxygenation of 1,1-dimethylcyclopropane: evidence for radical and carbocationic intermediates. Biochemistry, 1990, 29(7): 1696-1700.
[169] 崔金山,李海山,张淼,张玉敏,段志文.丙烯腈对DNA交联作用研究.中国工业医学杂志,2004,17(1):18-20.
[170] T. Shono, K. Ohsawa, J. E. Casida. Metabolism of trans- and cis-permethrin, trans- and cis-cypermethrin, and decamethrin by microsomal enzymes. Journal of Agricultural and Food Chemistry, 1979, 27(2): 316-325.
[171] R. F. Henderson. Species differences in the metabolism of olefins: implications for risk assessment. Chemico-Biological Interactions, 2001, 135-136: 53-64.
[172] 黄俊勇,冷欣夫.离体鼠肝细胞及P-450酶系与拟除虫菊酯类杀虫剂的相互作用.动物学报,1993,39(4):418—423.
[173] 石俊,张志.体内一体外试验检测不同组织中化学致癌物诱导的程序外DNA合成.癌变·畸变·突变,1995,7(2):69—74.
[174] W. M. Generoso, G. A. Sega, A. M. Lockhart, L. A. Hughes, K. T. Cain, N. L. A. Cacheiro, M. D. Shelby. Dominant lethal mutations, heritable translocations, and unscheduled DNA synthesis induced in male mouse germ cells by glycidamide, a metabolite of acrylamide. Mutation Research, 1996, 371(3-4): 175-183.
[175] 吕群,译.样品研究设计.见:戴维·布鲁西克(D.Brusick),原著.吕群,强义国,江绍慧,泽.赵寿元,校.遗传毒理学原理(Principles of Genetic Toxicology).上海:复旦大学出版社,1987.New York:Plenum Press,1980.p:218-221.
[176] V. Bianchi, E. Pontis, P. Richard. Changes of deoxyribonucleoside triphosphate pools induced by hydroxyurea and their relation to DNA synthesis. Journal of Biological Chemistry, 1986, 261: 16037-16042.
[177] S. -H. Ye, W. Zhou, J. Song, B. -C. Peng, D. Yuan, Y. -M. Lu, P. -P. Qi. Toxicity and health effects of vehicle emissions in Shanghai. Atmospheric Environment, 1999, 34(3): 419-429.
[178] J. Surralles, N. Xamena, A. Creus, R. Marcos. The suitability of the micronucleus assay in human lymphocytes as a new biomarker of excision repair. Mutation Research, 1995, 342(1-2): 43-59.
[179] 施正政,余应年.DNA甲基化与癌.实用肿瘤杂志,1990,5(4):247-249.
[180] 肖文华,刘为纹.DNA甲基化异常与肿瘤研究现状.肿瘤,1995,15(3):297-300.
[181] L. Tao, P. M. Kramer, R. Ge, M. A. Pereira. Effect of dichloroacetic acid and trichloroacetie acid on DNA methylation in liver and tumors of female B6C3F1 mice. Toxicological Sciences, 1998, 43(2): 139-144.
[182] R. Del Gaudio, R. Di Giaimo, G. Geraci. Genome methylation of the marine annelid worm Chaetopterus variopedatus: methylation of a CpG in an expressed HI histone gene. FEBS Letters, 1997, 417(1): 48-52.
[183] D. Chakrabarty, K. W. Yu, K. Y. paek. Detection of DNA methylation changes during somatic embryogenesis of Siberian ginseng (Eleuterococcus senticosus). Plant Science, 2003, 165(1): 61-68.
[184] M. Szyf. Targeting DNA methylation in cancer. Ageing Research Reviews, 2003, 2(3): 299-328.
[185] 曹树义,赵力军,汤乃军,王春华.氯乙烯诱变性研究.职业与健康,2005,21(3):447-448.
[186] 肖卫,王振全,李芝兰.丙烯腈雄性生殖毒性作用的调查与实验研究.中国公共卫生,2001,17(5):402-403.
[187] 江俊康,翁诗君.苯对雄性小鼠生殖系统的影响.中国工业医学杂志,2004,17(2):94—96.
[188] 王文祥,廖惠珍,曹建平,王章敬,林崴.亚慢性镉暴露对雄性大鼠生殖毒性的研究.中国公共卫生,2004,20(5):562-563.
[189] 金龙金,董杰影,张军明.小剂量氯化汞对小鼠的生殖毒性.环境与健康杂志,2004,21(2):75-77.
[190] 宣登峰,易建华,画伟.锰对小鼠精子的损害作用.工业卫生与职业病,2002,28(1):17-19.
[191] 朱心强,郑一凡,张群卫,姜槐,黄幸纾.硫丹对成年大鼠生精功能的影响和氧化损伤.中国约理学与毒理学杂志,2002,16(5):391-395.
[192] 谈立峰,孙雪照,李燕南,吉俊敏,王茜丽,陈龙生,卞倩,王守林.甲萘威农药生产职业暴露对男工精子和精液质量的影响.中华劳动卫生职业病杂志,2005,23(2):87—90.
[193] 李东阳,让蔚清,谢红卫,贺栋梁,龙鼎新.烹调油烟对雄性大鼠的生殖毒性.环境与健康杂志,2005,22(1):37-39.