三氯乙烯对HepG2细胞的遗传毒性及氧化应激机制的研究
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摘要
目的:三氯乙烯(trichloroethylene, TCE)是一种易挥发的不饱和脂肪族卤代烃类有机溶剂。TCE常用作金属去脂剂、除油剂和有机溶剂,业已被广泛应用在五金、电子、玩具、造纸、印刷、干洗、油漆、纺织、有机合成等诸多生产加工过程中。由于其在各行业的大规模应用及其本身所具有的挥发性和微量溶水性特征,TCE已成为全球最重要的有机污染物之一,广泛存在于城市大气、土壤、地表水、地下水等环境介质中。人群流行病学调查结果显示,美国、中国、德国一般人群的血和尿中均发现有一定量的TCE。
动物实验现已证实TCE具有致癌性,但由于人群流行病学研究资料有限,至今尚未能就TCE对人类的致癌性作出明确的结论。尽管如此,国际癌症研究中心(IARC)仍于1995年将TCE从Ⅲ类(非人类致癌物)提升为ⅡA类(对人类很可能致癌类)。近年来一些研究显示,TCE的毒性与其体内代谢过程密切相关,具有种属特异性;TCE可以引发实验动物及职业接触者脂质过氧化水平的升高。考虑到肝脏的靶器官地位以及细胞色素P450酶系在TCE所致机体毒性中的重要作用,本实验选用人类来源的肝脏肿瘤细胞HepG2细胞系作为体外试验系统,研究TCE的遗传毒效应及其与氧化应激之间的关系。HepG2细胞来源于人类肝胚细胞瘤,所含生物转化代谢酶与人正常肝实质细胞具有同源性,它保留了较完整的生物转化代谢I相和II相酶,是检测外来化学物遗传毒性的理想细胞系。
本研究旨在探讨TCE的遗传毒性及其可能机制,补充TCE的遗传毒性研究资料,从而为评价其对人类健康的潜在危害提供实验室依据。
方法:以HepG2细胞株作为试验系统。采用单细胞凝胶电泳(SCGE)试验和微核试验(MNT)检测细胞DNA损伤和染色体损伤。为探讨其遗传毒性机制,用硫代巴比妥酸反应物(TBARS)测定法检测细胞内脂质过氧化水平,以免疫组化方法检测细胞内8-羟基脱氧鸟苷(8-OHdG)的表达水平。用噻唑蓝(MTT)法检测细胞存活率,以邻苯二甲醛荧光素(OPT)比色法测定细胞内GSH水平,采用DL-甲硫氨酸磺酰亚胺(BSO)和N-乙酰半胱氨酸(NAC)干预法测定细胞内GSH水平对TCE所致DNA损伤效应的影响。用SPSS统计软件包对实验结果进行统计分析。
结果:0.5-4.0 mM的TCE作用HepG2细胞1 h,可引起实验组细胞DNA链断裂,形成彗星样脱尾,彗星的尾长、尾矩(尾矩=尾长×尾部DNA含量%)随TCE染毒剂量的增加而增长。相同浓度的TCE作用于HepG2细胞24 h后可引起细胞微核率明显升高,呈剂量依赖关系。随着TCE染毒剂量的增加,细胞内TBARS增多,8-OHdG表达水平增强。0.25-10 mM的TCE作用于HepG2细胞8 h,各剂量组细胞存活率与对照组相比无明显差异。采用150μM BSO预处理HepG2细胞20 h使细胞内GSH耗竭,可明显增强TCE对HepG2细胞的细胞毒性及对DNA的损伤,且有剂量依赖关系;采用5 mM NAC提高HepG2细胞内GSH水平,则可明显地甚至完全抑制TCE引起HepG2细胞DNA链断裂的效应。
结论:TCE对HepG2细胞具有遗传毒性。TCE可能通过引起HepG2细胞的氧化应激,导致脂质过氧化水平的升高以及8-OHdG表达的增强。细胞内重要的抗氧化剂GSH,对防御TCE引起HepG2细胞的DNA损伤具有重要作用。
Introduction: Trichloroethylene (TCE) is an important vapor degreaser for the cold cleaning of fabricated metal parts and a general solvent for fats, waxes, resins, oils, rubber, cellulose esters and ethers, paints, and varnishes. Owing to its widespread use, partial water solubility and volatility, TCE has been found extensively in the environmental medium, such as the air, soil, surface water, and groundwater. The data of epidemiological studies reveal that TCE could be detected in blood and urine of the residents in many countries.
TCE is known an animal carcinogen in rodents. In 1995, the International Agency for Research on Cancer (IARC) classified it to be "probably carcinogenic in humans" (group 2A) both on the basis of limited evidence for carcinogenicity in humans and a sufficient evidence for carcinogenicity in experimental animals. Recently, some studies revealed that there are species differences in response to trichloroethylene. The toxicity of TCE is dependent on the metabolism by cytochrome P450 (P450)-dependent oxidation and GSH conjugation. TCE could increase the level of lipid peroxidation in the tested cells of experimental animals and TCE exposed population. Considering that liver is the potential tumor target site of TCE in human and P450 play an important role in the oxidation metabolism of TCE in this organ, we selected HepG2 cells as the experimental system in vitro in our study. The HepG2 cell line retained many of the functions of normal liver cells and expresses the activities of several phases I and II xenobiotic metabolizing enzymes that play key roles in the activation and/or detoxification of DNA-reactive carcinogens. It has been shown to be a suitable system for genotoxicity testing.
The aim of this study was to assess the genotoxic effects of TCE and, moreover, to explore the role of oxidative stress in TCE-induced genotoxicity. We hope the results could give some useful information for the safety assessment to humans on TCE.
Methods:HepG2 cells were selected as test system. We used the single cell gel electrophoresis assay (SCGE) in addition to the micronucleus test (MNT) to study the genotoxic effects of TCE. Since the molecular mechanism of DNA damage by TCE may involve the oxidative stress, we evaluated the level of lipid peroxidation by measurement of thiobarbituric acid–reactive substances (TBARS). In addition, Hydroxydeoxyguanosine (8-OHdG), which is a reliable marker for oxidative DNA damage, was also measured by immunoperoxidase staining analysis. To explore the role of GSH in TCE-induced DNA damage, the intracellular GSH level in HepG2 cells was monitored with o-phthalaldehyde (OPT) assay. DL-buthionine sulphoximine (BSO) and N-acetylcysteine (NAC) were used to modulate the level of GSH in HepG2 cells, and the effects of GSH on TCE-induced DNA damage were determined by the SCGE. Furthermore, the effect of GSH depletion on cytotoxicity of TCE in HepG2 cells was examined by the cell viability, using the methyl thiazol tetrazolium bromide (MTT) assay. The data were statistically analyzed by SPSS v 13.0 software.
Results: In the SCGE and MNT, TCE increased the DNA migration and the MN frequencies in a dose-dependent manner at all tested concentrations (0.5-4 mM, P < 0.05 or 0.01), respectively. The formation of TBARS was observed in HepG2 cells exposed to TCE. With the increasing of TCE concentration, the staining intensity of 8-OHdG increased obviously. There was no significant decrease in viability of HepG2 cells over an 8 h exposure to TCE concentration ranging from 0.25 to 10 mM. However, HepG2 cells became more susceptible to TCE at 8 h after pretreated with BSO (150μM) for 20 h and produced remarkable cytotoxic effects at concentrations above 4 mM. In BSO-pretreated HepG2 cells, TCE-induced significantly more DNA strand breaks than that in corresponding control cells. Co-treatment with NAC almost completely prevented the formation of TCE-induced DNA strand breaks at all tested concentrations.
Conclusion: TCE could be genotoxic to HepG2 cell. TCE exerts genotoxic effects in HepG2 cells, probably through DNA damage by oxidative stress; GSH, as a main intracellular antioxidant, is responsible for cellular defense against TCE-induced DNA damage.
动物实验现已证实TCE具有致癌性,但由于人群流行病学研究资料有限,至今尚未能就TCE对人类的致癌性作出明确的结论。尽管如此,国际癌症研究中心(IARC)仍于1995年将TCE从Ⅲ类(非人类致癌物)提升为ⅡA类(对人类很可能致癌类)。近年来一些研究显示,TCE的毒性与其体内代谢过程密切相关,具有种属特异性;TCE可以引发实验动物及职业接触者脂质过氧化水平的升高。考虑到肝脏的靶器官地位以及细胞色素P450酶系在TCE所致机体毒性中的重要作用,本实验选用人类来源的肝脏肿瘤细胞HepG2细胞系作为体外试验系统,研究TCE的遗传毒效应及其与氧化应激之间的关系。HepG2细胞来源于人类肝胚细胞瘤,所含生物转化代谢酶与人正常肝实质细胞具有同源性,它保留了较完整的生物转化代谢I相和II相酶,是检测外来化学物遗传毒性的理想细胞系。
本研究旨在探讨TCE的遗传毒性及其可能机制,补充TCE的遗传毒性研究资料,从而为评价其对人类健康的潜在危害提供实验室依据。
方法:以HepG2细胞株作为试验系统。采用单细胞凝胶电泳(SCGE)试验和微核试验(MNT)检测细胞DNA损伤和染色体损伤。为探讨其遗传毒性机制,用硫代巴比妥酸反应物(TBARS)测定法检测细胞内脂质过氧化水平,以免疫组化方法检测细胞内8-羟基脱氧鸟苷(8-OHdG)的表达水平。用噻唑蓝(MTT)法检测细胞存活率,以邻苯二甲醛荧光素(OPT)比色法测定细胞内GSH水平,采用DL-甲硫氨酸磺酰亚胺(BSO)和N-乙酰半胱氨酸(NAC)干预法测定细胞内GSH水平对TCE所致DNA损伤效应的影响。用SPSS统计软件包对实验结果进行统计分析。
结果:0.5-4.0 mM的TCE作用HepG2细胞1 h,可引起实验组细胞DNA链断裂,形成彗星样脱尾,彗星的尾长、尾矩(尾矩=尾长×尾部DNA含量%)随TCE染毒剂量的增加而增长。相同浓度的TCE作用于HepG2细胞24 h后可引起细胞微核率明显升高,呈剂量依赖关系。随着TCE染毒剂量的增加,细胞内TBARS增多,8-OHdG表达水平增强。0.25-10 mM的TCE作用于HepG2细胞8 h,各剂量组细胞存活率与对照组相比无明显差异。采用150μM BSO预处理HepG2细胞20 h使细胞内GSH耗竭,可明显增强TCE对HepG2细胞的细胞毒性及对DNA的损伤,且有剂量依赖关系;采用5 mM NAC提高HepG2细胞内GSH水平,则可明显地甚至完全抑制TCE引起HepG2细胞DNA链断裂的效应。
结论:TCE对HepG2细胞具有遗传毒性。TCE可能通过引起HepG2细胞的氧化应激,导致脂质过氧化水平的升高以及8-OHdG表达的增强。细胞内重要的抗氧化剂GSH,对防御TCE引起HepG2细胞的DNA损伤具有重要作用。
Introduction: Trichloroethylene (TCE) is an important vapor degreaser for the cold cleaning of fabricated metal parts and a general solvent for fats, waxes, resins, oils, rubber, cellulose esters and ethers, paints, and varnishes. Owing to its widespread use, partial water solubility and volatility, TCE has been found extensively in the environmental medium, such as the air, soil, surface water, and groundwater. The data of epidemiological studies reveal that TCE could be detected in blood and urine of the residents in many countries.
TCE is known an animal carcinogen in rodents. In 1995, the International Agency for Research on Cancer (IARC) classified it to be "probably carcinogenic in humans" (group 2A) both on the basis of limited evidence for carcinogenicity in humans and a sufficient evidence for carcinogenicity in experimental animals. Recently, some studies revealed that there are species differences in response to trichloroethylene. The toxicity of TCE is dependent on the metabolism by cytochrome P450 (P450)-dependent oxidation and GSH conjugation. TCE could increase the level of lipid peroxidation in the tested cells of experimental animals and TCE exposed population. Considering that liver is the potential tumor target site of TCE in human and P450 play an important role in the oxidation metabolism of TCE in this organ, we selected HepG2 cells as the experimental system in vitro in our study. The HepG2 cell line retained many of the functions of normal liver cells and expresses the activities of several phases I and II xenobiotic metabolizing enzymes that play key roles in the activation and/or detoxification of DNA-reactive carcinogens. It has been shown to be a suitable system for genotoxicity testing.
The aim of this study was to assess the genotoxic effects of TCE and, moreover, to explore the role of oxidative stress in TCE-induced genotoxicity. We hope the results could give some useful information for the safety assessment to humans on TCE.
Methods:HepG2 cells were selected as test system. We used the single cell gel electrophoresis assay (SCGE) in addition to the micronucleus test (MNT) to study the genotoxic effects of TCE. Since the molecular mechanism of DNA damage by TCE may involve the oxidative stress, we evaluated the level of lipid peroxidation by measurement of thiobarbituric acid–reactive substances (TBARS). In addition, Hydroxydeoxyguanosine (8-OHdG), which is a reliable marker for oxidative DNA damage, was also measured by immunoperoxidase staining analysis. To explore the role of GSH in TCE-induced DNA damage, the intracellular GSH level in HepG2 cells was monitored with o-phthalaldehyde (OPT) assay. DL-buthionine sulphoximine (BSO) and N-acetylcysteine (NAC) were used to modulate the level of GSH in HepG2 cells, and the effects of GSH on TCE-induced DNA damage were determined by the SCGE. Furthermore, the effect of GSH depletion on cytotoxicity of TCE in HepG2 cells was examined by the cell viability, using the methyl thiazol tetrazolium bromide (MTT) assay. The data were statistically analyzed by SPSS v 13.0 software.
Results: In the SCGE and MNT, TCE increased the DNA migration and the MN frequencies in a dose-dependent manner at all tested concentrations (0.5-4 mM, P < 0.05 or 0.01), respectively. The formation of TBARS was observed in HepG2 cells exposed to TCE. With the increasing of TCE concentration, the staining intensity of 8-OHdG increased obviously. There was no significant decrease in viability of HepG2 cells over an 8 h exposure to TCE concentration ranging from 0.25 to 10 mM. However, HepG2 cells became more susceptible to TCE at 8 h after pretreated with BSO (150μM) for 20 h and produced remarkable cytotoxic effects at concentrations above 4 mM. In BSO-pretreated HepG2 cells, TCE-induced significantly more DNA strand breaks than that in corresponding control cells. Co-treatment with NAC almost completely prevented the formation of TCE-induced DNA strand breaks at all tested concentrations.
Conclusion: TCE could be genotoxic to HepG2 cell. TCE exerts genotoxic effects in HepG2 cells, probably through DNA damage by oxidative stress; GSH, as a main intracellular antioxidant, is responsible for cellular defense against TCE-induced DNA damage.
引文
1. Fahrig R, Madle S, Baumann H. Genetic toxicology of trichloroethylene (TCE). Mutat. Res. 1995,340 (1): 1-36.
2. Agency for Toxic Substances and Disease Registry(ATSDR). Public Health Statement for Trichloroethylene. Toxicological Profile for Trichloroethylene. 1997.
3. Holton WC. Popular demand. Environ Health Perspect. 1998,106(9):A438-440
4. Anna CH, Maronpot RR, Pereira MA, Ras protooncogene activation in dichloroacetic acid-, trichloroethylene- and tetrachloroethylene-induced liver tumors in B6C3F1 mice. Carcinogenesis 1994, 15 (10):2255-2261.
5. National Toxicology Program. NTP Carcinogenesis Studies of Trichloroethylene (Without Epichlorohydrin) (CAS No. 79-01-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Natl. Toxicol. Program. Tech.Rep.Ser. 1990, 243:1-174.
6. Rhomberg LR. Dose-response analyses of the carcinogenic effects of trichloroethylene in experimental animals. Environ. Health Perspect. 2000,108 (Suppl 2) :343-358.
7. International Agency for Research on Cancer (IARC). Dry cleaning, some chlorinated solvents, and other industrial chemicals. IARC Monogr. Eval. Carcinog. Risks Hum. 1995, 63:75-158.
8. Motohashi N, Nagashima H, Molnár J. Trichloroethylene .I. Carcinogenicity of trichloroethylene. In Vivo. 1999, 13 (3):211-214.
9. Walles SAS., Induction of single strand breaks in DNA of mice by trichloroethylene and tetrachloroethylene. Toxicol. Lett. 1986, 31 (1): 31-35.
10. Nelson M.A, Bull R.J. Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Toxicol. Appl. Pharmacol. 1988, 94 (1):45-54.
11. Mazzullo M, Bartoli S, Bonora B, et al. In vivo and in vitro interaction of trichloroethylene with macromolecules from various organs of rat and mouse. Res Commun. Chem. Pathol. Pharmacol. 1992, 76:192-208.
12. Robbiano L, Baroni D, Carrozzino R, et al. DNA damage and micronuclei induced in rat and human kidney cells by six chemicals carcinogenic to the rat kidney. Toxicology 2004, 204 (2-3):187–195.
13. Sujatha TV, Hegde MJ. C-mitotic effects of trichloroethylene (TCE) on bonemarrow cells of mice. Mutat. Res. 1998, 413(2):151-158.
14. Wang JL, Chen WL, Tsai SY, et al. An in vitro model for evaluation of vaporous toxicity of trichloroethylene and tetrachloroethylene to CHO-K1 cells. Chem. Biol. Interact. 2001,137 (2):139-154.
15. Hrelia P, Maffei F, Vigagni F, et al. Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice. Environ. Health Perspect. 1994, 102( Suppl 9):31-34.
16. Channel SR, Latendresse JR, Kidney JK, et al. A subchronic exposure to trichloroethylene causes lipid peroxidation and hepatocellular proliferation in male B6C3F1 mouse liver. Toxicol. Sci. 1998, 43 (2):145-154.
17. Toraason M, Clark J, Dankovic D, et al. Oxidative stress and DNA damage in Fischer rats following acute exposure to trichloroethylene or perchloroethylene. Toxicology 1999,138 (1):43-53.
18. Ogino K, Hobara T, Kobayashi H, et al. Lipid peroxidation induced by trichloroethylene in rat liver. Bull. Environ. Contam. Toxicol. 1991, 46 (3):417-421.
19.杨翠婵,李伯灵,邹志方.低剂量三氯乙烯对作业工人脂质过氧化作用的影响.华南预防医学. 2002, 28(3):23-24.
20.黄锦生,陈惠珍,吴平方,等.低浓度三氯乙烯对人体抗氧化物酶系统影响.中国公共卫生. 2002, 18(3):282-283.
21. Lash LH, Fisher JW, Lipscomb JC, et al. Metabolism of trichloroethylene. Environ. Health Perspect. 2000,108 (Suppl 2):177-200.Review.
22. Lash LH, Putt DA, Brashear WT, at al. Identification of S-(1,2-dichlorovinyl)glutathione in the blood of human volunteers exposed to trichloroethylene. J Toxicol Environ Health A.1999, 56(1):1-21.
23. Knowles BB, Howe CC, Aden DP. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 1980,209 (4455):497–499.
24. Knasmüller S, Parzefall W, Sanyal R, et al. Use of metabolically competent human hepatoma cells for the detection of mutagens and antimutagens. Mutat. Res. 1998,402 (1-2):185–202.
25. Mersch-Sundermann V, Knasmüller S, Wu XJ, et al. Use of a human-derived liver cell line for the detection of cytoprotective, antigenotoxic and cogenotoxic agents. Toxicology 2004,198 (1-3):329–340.
26. Singh NP, Stephens RE. Microgel electrophoresis: sensitivity, mechanisms, and DNA electrostretching, Mutat. Res. 1997,383 (3):167–175.
27. Natarajan AT, Darroudi F. Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens. Mutagenesis 1991, 5:399–403.
28. Kirsch-Volders M, Sofuni T, Aardema M., et al. Report from the in vitro micronucleus assay working group. Environ. Mol. Mutagen. 2000, 35(3): 167–172.
29. Leal LKAM, Junior HVN, Cunhaa GMA, et al. Amburoside, a glucoside from Amburana cearensis , protects mesencephalic cells against 6-hydroxydopamine-induced neurotoxicity . Neurosci. Lett . 2005 , 388 (2) : 86–90.
30. Yarborough A, Zhang YJ, Hsu TM, et al. Immunoperoxidase detection of
8-hydroxydeoxygua-nosine in aflatoxin B1-treated rat liver and human oral mucosal cells. Cancer Res. 1996, 56 (4):683–688.
31. Romano G, Sgambato A, Mancini R, et al. 8-hydroxy-2'-deoxyguanosine in cervical cells: correlation with grade of dysplasia and human papillomavirus infection. Carcinogenesis, 2000, 21(6):1143-1147.
32. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65(1-2):55-63.
33. Hissin PJ, Hilf R. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 1976, 74 (1):214–226.
34. Lash LH, Qian W, Putt DA, et al. Glutathione conjugation of trichloroethylene in rats and mice: sex-, species-, and tissue-dependent differences. Drug Metab. 1998, 26:12-19.
35. Lash LH, Lipscomb JC, Putt DA, et al. Glutathione conjugation of trichloroethylene in human liver and kidney: kinetics and individual variation. Drug Metab . 1999, 27:351-359.
36. Kirsch VM, Elhajouji A, Cundari E, et al. The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously mitotic delay, apoptosis, chromosome breakage, chromosome loss and non-disjunction. Mutat. Res. 1997, 392(1-2): 19-30.
37. Fenech M. The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. Mutat. Res. 1993, 285(1):35-44.
38. Fairbairn DW, Olive PL, O’Neill KL. The comet assay: a comprehensive review. Mutat. Res. 1995, 339(1):37–59.
39.刘晓麒,曹恩华.脂质过氧化引起的DNA损伤研究进展.生物化学与生物物理进展.1994,21(3):218-221.
40. Halliwell B. Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward? Cardiovasc Res. 2000,47 (3):410-418.
41. Atkinson A, Meeks RG, Roy D. Increased oxidative stress in the liver of mice treated with trichloroethylene. Biochem Mol. Biol. Int.1993, 31(2):297-304.
42.张锦周,黄海雄,庄志雄,等.三氯乙烯急性染毒对大鼠肝脂质过氧化的影响.中国公共卫生. 2000,16(4):308-309.
43. Watanabe S, Fukui T. Suppressive effect of curcumin on trichloroethylene-Induced oxidative stress. J. Nutr. Sci. Vitaminol. 2000,46 (5):230-234.
44. Kasai H, Nishimura S. Hydroxylation of guanine in nucleoides and DNA at the C-8 position by heated glucose and oxygen radical-forming agents. Environ Health Perspect. 1986,67: 111-116.
45. Shigenaga MK, Ames BN. Assays for 8-hydroxy-2'-deoxyguanosine: a biomarker of in vivo oxidative DNA damage. Free Radic. Biol. Med.1991,10(3-4):211-216.
46. Kaneko T, Tahara S, Matsuo M. Non-linear accumulation of 8-hydroxy- 2’-deoxyguannsine, a marker of oxidative DNA damage during aging. Toxicol Appol Pharmacol. 1997, 147(1): 9-14.
47. Cheng KC, Cahill DS, Kasai H, et al. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G–T and A–C substitutions. J. Biol. Chem. 1992, 267 (1):166–172.
48. Moriya M. Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G?C→T?A transversions in simian kidney cells. Proc. Natl. Acad. Sci. U. S. A. 1993, 90 (3): 1122–1126.
49. Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2'- deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat. Res. 1997, 387(3): 147–163.
50. Henle ES, Linn S. Formation, prevention and repair of DNA damage by iron/hydrogen peroxide. J. Biol. Chem.1997, 272(31): 19095–19098.
51. Murata Y, Amao M, Yoneda J, et al. Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging. Mol. Immunol. 2002, 38(10):747-757.
1. Fahrig R, Madle S, Baumann H. Genetic toxicology of trichloroethylene (TCE). Mutat. Res. 1995,340 (1): 1-36.
2. Agency for Toxic Substances and Disease Registry(ATSDR). Public Health Statement for Trichloroethylene. Toxicological Profile for Trichloroethylene. 1997.
3. Holton WC. Popular demand. Environ Health Perspect. 1998,106(9):A438-440.
4. Anna CH, Maronpot RR, Pereira MA, et al. Ras protooncogene activation in dichloroacetic acid-, trichloroethylene- and tetrachloroethylene-induced liver tumors in B6C3F1 mice, Carcinogenesis 1994, 15 (10):2255-2261.
5. National Toxicology Program. NTP Carcinogenesis Studies of Trichloroethylene (Without Epichlorohydrin) (CAS No. 79-01-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Natl. Toxicol. Program. Tech.Rep.Ser.1990, 243:1-174.
6. Rhomberg LR. Dose-response analyses of the carcinogenic effects of trichloroethylene in experimental animals. Environ. Health Perspect. 2000,108 (Suppl 2):343-358.
7. International Agency for Research on Cancer (IARC). Dry cleaning, some chlorinated solvents, and other industrial chemicals, IARC Monogr. Eval. Carcinog. Risks Hum. 1995,63:75-158.
8.夏元洵.化学物质毒性全书.上海:上海科学技术文献出版社.1991,318
9. Lash LH, Fisher JW, Lipscomb JC, et al. Metabolism of trichloroethylene. Environ. Health Perspect. 2000,108 (Suppl 2):177-200.Review.
10. Lash LH, Putt DA, Brashear WT, at al. Identification of S-(1,2-dichlorovinyl) glutathione in the blood of human volunteers exposed to trichloroethylene. J. Toxicol. Environ. Health A. 1999, 56(1):1-21.
11. Motohashi N, Nagashima H, Molnár J. Trichloroethylene .I. Carcinogenicity of trichloroethylene. In Vivo. 1999, 13 (3): 211-214.
12.张锦周,黄海雄,黄钰,等.三氯乙烯对鼠伤寒沙门氏菌的致突变实验.职业与健康. 2002,18(3):2-4.
13. NTP Toxicology and Carcinogenesis Studies of Trichloroethylene (CAS No. 79-01-6) in Four Strains of Rats (ACI, August, Marshall, Osborne-Mendel) (Gavage Studies).National Toxicology Program. Natl Toxicol Program. Tech. Rep. Ser. 1988, 273:1-299.
14.蒋东方.微核试验在职业人群接触危害评价应用中的研究.中国职业医学.2000, 27(4):43-44.
15. Sujatha TV, Hegde MJ. C-mitotic effects of trichloroethylene (TCE) on bone marrow cells of mice. Mutat. Res. 1998,413 (2):151-158.
16. Hrelia P, Maffei F, Vigagni F, et al. Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice. Environ. Health Perspect. 1994 ,102(Suppl 9):31-34.
17. Wang JL, Chen WL, Tsai SY, et al. An in vitro model for evaluation of vaporous toxicity of trichloroethylene and tetrachloroethylene to CHO-K1 cells. Chem. Biol. Interact. 2001,137 (2):139-154.
18. Robbiano L, Baroni D, Carrozzino R, et al. DNA damage and micronuclei induced in rat and human kidney cells by six chemicals carcinogenic to the rat kidney. Toxicology 2004, 204 (2-3):187–195.
19. Allen JW, Collins BW, Fvansky PA. Spermatid micronucleus analyses of trichloroethylene and chloral hydrate effects in mice. Mutat. Res.1994, 323(1-2):81-88.
20.晁斌,练海泉,王家骥,等.三氯乙烯对职业人群遗传指标的影响.职业卫生与应急救治. 2005, 23 (1):2-3.
21.陈雯,徐雷,邓丽霞,等.三氯乙烯对接触工人外周血微核率的影响.中国职业医学. 2000, 27 (5): 9.
22.阎莉,徐栋,王春燕,等.三氯乙烯对接触工人外周血淋巴细胞微核的影响.中国工业医学杂志.2002,15 (2):123
23.黄海雄,张锦周,黄址,等.三氯乙烯染毒小鼠骨髓微核试验观察.职业与健康. 2002,18(4): 35-36.
24. Kligerman AD, Bryant MF, Doerr CL, et al. Inhalation studies of the genotoxicity of trichloroethylene to rodents. Mutat. Res. 1994,322 (2):87-96.
25. Matsuoka A, Yamakage K, Kusakabe H, et al. Re-evaluation of chromosomal aberration induction on nine mouse lymphoma assay‘unique positive’NTP carcinogens. Mutat. Res. 1996, 369(3-4):243-252.
26.邓丽霞,陈雯,徐雷,等.三氯乙烯接触工人外周血淋巴细胞染色体畸变分析.中国工业医学杂志. 2001, 14(5):275-277.
27. Crebelli R, Carere A. Genetic toxicology of 1,1,2-trichloroethylene. Mutat. Res. 1989, 221(1):11-37.
28. Walles SAS. Induction of single strand breaks in DNA of mice bytrichloroethylene and tetrachloroethylene. Toxicol. Lett. 1986, 31 (1):31-35.
29. Nelson MA, Bull RJ. Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Toxicol. Appl. Pharmacol. 1988, 94 (1):45-54.
30.唐国慧,庄志雄,张锦周.三氯乙烯诱发小鼠及人外周血有核细胞DNA链断裂.中华劳动卫生职业病杂志. 1997, 15(3):146-149.
31.王家骥,练海泉,胡明霞,等.三氯乙烯对职业人群的细胞遗传学效应.癌变·畸变·突变. 2003, 15(1):38-42.
32. Cunli Hu, Liping Jiang, Chengyan Geng, et al. Possible involvement of oxidative stress in trichloroethylene-induced genotoxicity in human HepG2 cells. Mutat.Res. 2008, 652(1): 88-94.
33. Gu JW, SelE B, Jalbert P, et a1.Induction of sister chromatide exchange by trichloroethylene and its metabolites. Toxicol. Eur. Res.1981, 3(2):63-67.
34. Seiji K, Jin C, Watanabe T, et al. Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene, trichloroethylene, or tetrachloroethylene, with reference to smoking habits. Int. Arch. Occup. Environ. Health 1990, 62(2):171-176.
35. Nagaya T, Ishikawa N, Hata H. Sister-chromatid exchanges in lymphocytes of workers exposed to trichloroethylene. Mutat. Res. 1989, 222(3):279-382.
36. Kautiainen A, Vogel JS, Turteltaub KW. Dose-dependent binding of trichloroethylene to hepatic DNA and protein at low doses in mice. Chem. Biol. Interact, 1997,106(2):109-121.
37. Halmes NC, Perkins EJ, McMillan DC, et al. Detection of trichloroethylene- protein adducts in rat liver and plasma. Toxicol. Lett.1997, 92(3):187-194.
38. Elfarra AA, Krause RJ, Last AR, et al. Species- and sex-related differences in metabolism of trichloroethylene to yield chloral and trichloroethanol in mouse, rat, and human liver microsomes. Drug Metab. Dispos.1998, 26(8):779-785.
39. Nakajima T, Kamijo Y, Usuda N, at al. Sex-dependent regulation of hepatic peroxisome proliferation in mice by trichloroethylene via peroxisome proliferator-activated receptor alpha (PPARalpha). Carcinogenesis.2000 21(4): 677-682.
40. Cummings BS, Lash H. Metabolism and toxicity of trichloroethylene and S-(1,2-dichloroviny1)-L-cysteine in freshly isolated human proximal tubular cells. Toxicol Sci. 2000, 53(2):458-466.
41. Cummings BS, Lasker JM, Lash LH. Expression of glutathione-dependent enzymes and cytochrome P450s in freshly isolated and primary cultures of proximal tubular cells from human kidney. J. Pharmacol. Exp. Ther. 2000, 293 (2):677-685.
42. Snawder JE, Lipscomb JC. Interindividual variance of cytochrome P450 forms in human hepatic microsomes: correlation of individual forms with xenobiotic metabolism and implications in risk assessment. Regul. Toxicol. Pharmacol. 2000, 32 (2):200-209.
43. Kato Y, Asano Y, Cooper AJ. Inactivation of brain and kidney aspartate aminotranslerases by S-(1,2-dichlorovinyl)-L-cysteine and by S-(1,1,2,2,-tetrafluoroethyl)-L-cysteine . Dev . Neurosci. 1996, 18 (5-6):505-514.
44. Cummings BS, Parker JC, Lash LH. Role of cytochrome P450 glutathione S-transferase alpha in the metabolism and cytotoxicity of trichloroethylene in rat kidney. Biochem. Pharmacol. 2000, 59 (5):531-543.
45. Cummings BS, Lash LH. Cytochrome P450-Dependent Metabolism of Trichloroethylene in Rat kidney. Toxicol. Sci. 2001, 60(1):11-19.
46. Green T. Pulmonary toxicity and carcinogenicity of trichloroethy-lene: Species differences and modes of action. Environ. Health Perspect. 2000,108 (Suppl 2): 261-264.
47. Bull RJ. Mode of action of liver tumor induction trichloroethylene and its metabolites, trichloroacetate and dichloroacetate. Environ. Health Perspect. 2000,108(Suppl 2):241-259.
48. Atkinson A, Meeks RG, Roy D. Increased oxidative stress in the liver of mice treated with trichloroethylene. Biochem. Mol. Biol. Int.1993, 31(2):297-304.
49. Steel GL, Pravecek TL, Carmichael AJ. Trichloroethylene metabolism in vitro: an CPR/SPI N trapping study. Hum. Exp. Toxicol.1996, 15(11): 878-884.
50.张锦周,黄海雄,庄志雄,等.三氯乙烯急性染毒对大鼠肝脂质过氧化的影响.中国公共卫生. 2000, 16(4):308-309.
51. Watanabe S, Fukui T. Suppressive effect of curcumin on trichloroethylene-Induced oxidative stress. J. Nutr. Sci. Vitaminol. 2000, 46 (5):230-234.
52.杨翠婵,李伯灵,邹志方.低剂量三氯乙烯对作业工人脂质过氧化作用的影响.华南预防医学. 2002, 28(3):23-24.
53.黄锦生,陈惠珍,吴平方,等.低浓度三氯乙烯对人体抗氧化物酶系统影响.中国公共卫生. 2002, 18(3):282-283.
54.方城.过氧化酶体与致癌的关系.国外医学卫生学分册. 2000, 27 (5):289-292
55. Klaunig JE, Babieh MA, Baetcke KP, et a1. PPARαagonist-induced rodent tumors: modes of action and human relevance. Crit. Rev. Toxicol. 2003, 33(6):655-780.
56. Dzhekova-Stojkova S, Bogdanska J, Stojkova Z. Peroxisome p roliferators: their biological and toxicological effects. Clin. Chem. Lab. Med. 2001, 39(6): 468-474.
57. Tao L, Ge R, Xie M, et al. Effect of trichloroethylene on DNA methylation and expression of early-intermediate protooncogenes in the liver of B6C3F1 mice. J Biochem. Mol. Toxicol. 1999, 13 (5):231-237.
58. Tao L,Yang S,Xie M,et al. Effect of trichloroethylene and its metabolites, dichloroacetic acid and trichloroacetic acid, on the methylation and expression of c-jun and c-myc protooncogenes in mouse liver: prevention by methionirne. Toxicol. Sci. 2000, 54 (2):399-407.
59. Tao L, Kramer PM, Ge R, et al. Effect of dichloroacetic acid and trichloroacetic acid on DNA methylation in liver and tumors of female B6C3F1 mice. Toxicol. Sci. 1998, 43 (2):139-144.
60. Bruning T, Bolt HM. Renal toxicity and carcinogenicity of trichloroethylene: key results,mechanisms,and controversies. Crit. Rev. Toxicol. 2000,30 (3):253-285
61. Schraml P, Zhaou M, Richter J. Analysis of kidney tumors in trichloroethylene exposed workers by comparative genomic hybridzation and DNA sequence analysis. Verh. Dtsch. Ges. Pathol. 1999,83:218-224.
62. Moore MM, Harrington BK. Mutagenicity of trichloroethylene and its metabolites: implications for the risk assessment of triehloroethylene. Environ. Health Perspect. 2000, 108(Suppl 2):215-223.
63. Lash LH, Parker JC, Modes of action of trichloroethylene for kidney tumorigenesis. Environ. Health Perspect. 2000, 108(Suppl 2):225-240.
2. Agency for Toxic Substances and Disease Registry(ATSDR). Public Health Statement for Trichloroethylene. Toxicological Profile for Trichloroethylene. 1997.
3. Holton WC. Popular demand. Environ Health Perspect. 1998,106(9):A438-440
4. Anna CH, Maronpot RR, Pereira MA, Ras protooncogene activation in dichloroacetic acid-, trichloroethylene- and tetrachloroethylene-induced liver tumors in B6C3F1 mice. Carcinogenesis 1994, 15 (10):2255-2261.
5. National Toxicology Program. NTP Carcinogenesis Studies of Trichloroethylene (Without Epichlorohydrin) (CAS No. 79-01-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Natl. Toxicol. Program. Tech.Rep.Ser. 1990, 243:1-174.
6. Rhomberg LR. Dose-response analyses of the carcinogenic effects of trichloroethylene in experimental animals. Environ. Health Perspect. 2000,108 (Suppl 2) :343-358.
7. International Agency for Research on Cancer (IARC). Dry cleaning, some chlorinated solvents, and other industrial chemicals. IARC Monogr. Eval. Carcinog. Risks Hum. 1995, 63:75-158.
8. Motohashi N, Nagashima H, Molnár J. Trichloroethylene .I. Carcinogenicity of trichloroethylene. In Vivo. 1999, 13 (3):211-214.
9. Walles SAS., Induction of single strand breaks in DNA of mice by trichloroethylene and tetrachloroethylene. Toxicol. Lett. 1986, 31 (1): 31-35.
10. Nelson M.A, Bull R.J. Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Toxicol. Appl. Pharmacol. 1988, 94 (1):45-54.
11. Mazzullo M, Bartoli S, Bonora B, et al. In vivo and in vitro interaction of trichloroethylene with macromolecules from various organs of rat and mouse. Res Commun. Chem. Pathol. Pharmacol. 1992, 76:192-208.
12. Robbiano L, Baroni D, Carrozzino R, et al. DNA damage and micronuclei induced in rat and human kidney cells by six chemicals carcinogenic to the rat kidney. Toxicology 2004, 204 (2-3):187–195.
13. Sujatha TV, Hegde MJ. C-mitotic effects of trichloroethylene (TCE) on bonemarrow cells of mice. Mutat. Res. 1998, 413(2):151-158.
14. Wang JL, Chen WL, Tsai SY, et al. An in vitro model for evaluation of vaporous toxicity of trichloroethylene and tetrachloroethylene to CHO-K1 cells. Chem. Biol. Interact. 2001,137 (2):139-154.
15. Hrelia P, Maffei F, Vigagni F, et al. Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice. Environ. Health Perspect. 1994, 102( Suppl 9):31-34.
16. Channel SR, Latendresse JR, Kidney JK, et al. A subchronic exposure to trichloroethylene causes lipid peroxidation and hepatocellular proliferation in male B6C3F1 mouse liver. Toxicol. Sci. 1998, 43 (2):145-154.
17. Toraason M, Clark J, Dankovic D, et al. Oxidative stress and DNA damage in Fischer rats following acute exposure to trichloroethylene or perchloroethylene. Toxicology 1999,138 (1):43-53.
18. Ogino K, Hobara T, Kobayashi H, et al. Lipid peroxidation induced by trichloroethylene in rat liver. Bull. Environ. Contam. Toxicol. 1991, 46 (3):417-421.
19.杨翠婵,李伯灵,邹志方.低剂量三氯乙烯对作业工人脂质过氧化作用的影响.华南预防医学. 2002, 28(3):23-24.
20.黄锦生,陈惠珍,吴平方,等.低浓度三氯乙烯对人体抗氧化物酶系统影响.中国公共卫生. 2002, 18(3):282-283.
21. Lash LH, Fisher JW, Lipscomb JC, et al. Metabolism of trichloroethylene. Environ. Health Perspect. 2000,108 (Suppl 2):177-200.Review.
22. Lash LH, Putt DA, Brashear WT, at al. Identification of S-(1,2-dichlorovinyl)glutathione in the blood of human volunteers exposed to trichloroethylene. J Toxicol Environ Health A.1999, 56(1):1-21.
23. Knowles BB, Howe CC, Aden DP. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 1980,209 (4455):497–499.
24. Knasmüller S, Parzefall W, Sanyal R, et al. Use of metabolically competent human hepatoma cells for the detection of mutagens and antimutagens. Mutat. Res. 1998,402 (1-2):185–202.
25. Mersch-Sundermann V, Knasmüller S, Wu XJ, et al. Use of a human-derived liver cell line for the detection of cytoprotective, antigenotoxic and cogenotoxic agents. Toxicology 2004,198 (1-3):329–340.
26. Singh NP, Stephens RE. Microgel electrophoresis: sensitivity, mechanisms, and DNA electrostretching, Mutat. Res. 1997,383 (3):167–175.
27. Natarajan AT, Darroudi F. Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens. Mutagenesis 1991, 5:399–403.
28. Kirsch-Volders M, Sofuni T, Aardema M., et al. Report from the in vitro micronucleus assay working group. Environ. Mol. Mutagen. 2000, 35(3): 167–172.
29. Leal LKAM, Junior HVN, Cunhaa GMA, et al. Amburoside, a glucoside from Amburana cearensis , protects mesencephalic cells against 6-hydroxydopamine-induced neurotoxicity . Neurosci. Lett . 2005 , 388 (2) : 86–90.
30. Yarborough A, Zhang YJ, Hsu TM, et al. Immunoperoxidase detection of
8-hydroxydeoxygua-nosine in aflatoxin B1-treated rat liver and human oral mucosal cells. Cancer Res. 1996, 56 (4):683–688.
31. Romano G, Sgambato A, Mancini R, et al. 8-hydroxy-2'-deoxyguanosine in cervical cells: correlation with grade of dysplasia and human papillomavirus infection. Carcinogenesis, 2000, 21(6):1143-1147.
32. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65(1-2):55-63.
33. Hissin PJ, Hilf R. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 1976, 74 (1):214–226.
34. Lash LH, Qian W, Putt DA, et al. Glutathione conjugation of trichloroethylene in rats and mice: sex-, species-, and tissue-dependent differences. Drug Metab. 1998, 26:12-19.
35. Lash LH, Lipscomb JC, Putt DA, et al. Glutathione conjugation of trichloroethylene in human liver and kidney: kinetics and individual variation. Drug Metab . 1999, 27:351-359.
36. Kirsch VM, Elhajouji A, Cundari E, et al. The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously mitotic delay, apoptosis, chromosome breakage, chromosome loss and non-disjunction. Mutat. Res. 1997, 392(1-2): 19-30.
37. Fenech M. The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. Mutat. Res. 1993, 285(1):35-44.
38. Fairbairn DW, Olive PL, O’Neill KL. The comet assay: a comprehensive review. Mutat. Res. 1995, 339(1):37–59.
39.刘晓麒,曹恩华.脂质过氧化引起的DNA损伤研究进展.生物化学与生物物理进展.1994,21(3):218-221.
40. Halliwell B. Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward? Cardiovasc Res. 2000,47 (3):410-418.
41. Atkinson A, Meeks RG, Roy D. Increased oxidative stress in the liver of mice treated with trichloroethylene. Biochem Mol. Biol. Int.1993, 31(2):297-304.
42.张锦周,黄海雄,庄志雄,等.三氯乙烯急性染毒对大鼠肝脂质过氧化的影响.中国公共卫生. 2000,16(4):308-309.
43. Watanabe S, Fukui T. Suppressive effect of curcumin on trichloroethylene-Induced oxidative stress. J. Nutr. Sci. Vitaminol. 2000,46 (5):230-234.
44. Kasai H, Nishimura S. Hydroxylation of guanine in nucleoides and DNA at the C-8 position by heated glucose and oxygen radical-forming agents. Environ Health Perspect. 1986,67: 111-116.
45. Shigenaga MK, Ames BN. Assays for 8-hydroxy-2'-deoxyguanosine: a biomarker of in vivo oxidative DNA damage. Free Radic. Biol. Med.1991,10(3-4):211-216.
46. Kaneko T, Tahara S, Matsuo M. Non-linear accumulation of 8-hydroxy- 2’-deoxyguannsine, a marker of oxidative DNA damage during aging. Toxicol Appol Pharmacol. 1997, 147(1): 9-14.
47. Cheng KC, Cahill DS, Kasai H, et al. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G–T and A–C substitutions. J. Biol. Chem. 1992, 267 (1):166–172.
48. Moriya M. Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G?C→T?A transversions in simian kidney cells. Proc. Natl. Acad. Sci. U. S. A. 1993, 90 (3): 1122–1126.
49. Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2'- deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat. Res. 1997, 387(3): 147–163.
50. Henle ES, Linn S. Formation, prevention and repair of DNA damage by iron/hydrogen peroxide. J. Biol. Chem.1997, 272(31): 19095–19098.
51. Murata Y, Amao M, Yoneda J, et al. Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging. Mol. Immunol. 2002, 38(10):747-757.
1. Fahrig R, Madle S, Baumann H. Genetic toxicology of trichloroethylene (TCE). Mutat. Res. 1995,340 (1): 1-36.
2. Agency for Toxic Substances and Disease Registry(ATSDR). Public Health Statement for Trichloroethylene. Toxicological Profile for Trichloroethylene. 1997.
3. Holton WC. Popular demand. Environ Health Perspect. 1998,106(9):A438-440.
4. Anna CH, Maronpot RR, Pereira MA, et al. Ras protooncogene activation in dichloroacetic acid-, trichloroethylene- and tetrachloroethylene-induced liver tumors in B6C3F1 mice, Carcinogenesis 1994, 15 (10):2255-2261.
5. National Toxicology Program. NTP Carcinogenesis Studies of Trichloroethylene (Without Epichlorohydrin) (CAS No. 79-01-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Natl. Toxicol. Program. Tech.Rep.Ser.1990, 243:1-174.
6. Rhomberg LR. Dose-response analyses of the carcinogenic effects of trichloroethylene in experimental animals. Environ. Health Perspect. 2000,108 (Suppl 2):343-358.
7. International Agency for Research on Cancer (IARC). Dry cleaning, some chlorinated solvents, and other industrial chemicals, IARC Monogr. Eval. Carcinog. Risks Hum. 1995,63:75-158.
8.夏元洵.化学物质毒性全书.上海:上海科学技术文献出版社.1991,318
9. Lash LH, Fisher JW, Lipscomb JC, et al. Metabolism of trichloroethylene. Environ. Health Perspect. 2000,108 (Suppl 2):177-200.Review.
10. Lash LH, Putt DA, Brashear WT, at al. Identification of S-(1,2-dichlorovinyl) glutathione in the blood of human volunteers exposed to trichloroethylene. J. Toxicol. Environ. Health A. 1999, 56(1):1-21.
11. Motohashi N, Nagashima H, Molnár J. Trichloroethylene .I. Carcinogenicity of trichloroethylene. In Vivo. 1999, 13 (3): 211-214.
12.张锦周,黄海雄,黄钰,等.三氯乙烯对鼠伤寒沙门氏菌的致突变实验.职业与健康. 2002,18(3):2-4.
13. NTP Toxicology and Carcinogenesis Studies of Trichloroethylene (CAS No. 79-01-6) in Four Strains of Rats (ACI, August, Marshall, Osborne-Mendel) (Gavage Studies).National Toxicology Program. Natl Toxicol Program. Tech. Rep. Ser. 1988, 273:1-299.
14.蒋东方.微核试验在职业人群接触危害评价应用中的研究.中国职业医学.2000, 27(4):43-44.
15. Sujatha TV, Hegde MJ. C-mitotic effects of trichloroethylene (TCE) on bone marrow cells of mice. Mutat. Res. 1998,413 (2):151-158.
16. Hrelia P, Maffei F, Vigagni F, et al. Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice. Environ. Health Perspect. 1994 ,102(Suppl 9):31-34.
17. Wang JL, Chen WL, Tsai SY, et al. An in vitro model for evaluation of vaporous toxicity of trichloroethylene and tetrachloroethylene to CHO-K1 cells. Chem. Biol. Interact. 2001,137 (2):139-154.
18. Robbiano L, Baroni D, Carrozzino R, et al. DNA damage and micronuclei induced in rat and human kidney cells by six chemicals carcinogenic to the rat kidney. Toxicology 2004, 204 (2-3):187–195.
19. Allen JW, Collins BW, Fvansky PA. Spermatid micronucleus analyses of trichloroethylene and chloral hydrate effects in mice. Mutat. Res.1994, 323(1-2):81-88.
20.晁斌,练海泉,王家骥,等.三氯乙烯对职业人群遗传指标的影响.职业卫生与应急救治. 2005, 23 (1):2-3.
21.陈雯,徐雷,邓丽霞,等.三氯乙烯对接触工人外周血微核率的影响.中国职业医学. 2000, 27 (5): 9.
22.阎莉,徐栋,王春燕,等.三氯乙烯对接触工人外周血淋巴细胞微核的影响.中国工业医学杂志.2002,15 (2):123
23.黄海雄,张锦周,黄址,等.三氯乙烯染毒小鼠骨髓微核试验观察.职业与健康. 2002,18(4): 35-36.
24. Kligerman AD, Bryant MF, Doerr CL, et al. Inhalation studies of the genotoxicity of trichloroethylene to rodents. Mutat. Res. 1994,322 (2):87-96.
25. Matsuoka A, Yamakage K, Kusakabe H, et al. Re-evaluation of chromosomal aberration induction on nine mouse lymphoma assay‘unique positive’NTP carcinogens. Mutat. Res. 1996, 369(3-4):243-252.
26.邓丽霞,陈雯,徐雷,等.三氯乙烯接触工人外周血淋巴细胞染色体畸变分析.中国工业医学杂志. 2001, 14(5):275-277.
27. Crebelli R, Carere A. Genetic toxicology of 1,1,2-trichloroethylene. Mutat. Res. 1989, 221(1):11-37.
28. Walles SAS. Induction of single strand breaks in DNA of mice bytrichloroethylene and tetrachloroethylene. Toxicol. Lett. 1986, 31 (1):31-35.
29. Nelson MA, Bull RJ. Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Toxicol. Appl. Pharmacol. 1988, 94 (1):45-54.
30.唐国慧,庄志雄,张锦周.三氯乙烯诱发小鼠及人外周血有核细胞DNA链断裂.中华劳动卫生职业病杂志. 1997, 15(3):146-149.
31.王家骥,练海泉,胡明霞,等.三氯乙烯对职业人群的细胞遗传学效应.癌变·畸变·突变. 2003, 15(1):38-42.
32. Cunli Hu, Liping Jiang, Chengyan Geng, et al. Possible involvement of oxidative stress in trichloroethylene-induced genotoxicity in human HepG2 cells. Mutat.Res. 2008, 652(1): 88-94.
33. Gu JW, SelE B, Jalbert P, et a1.Induction of sister chromatide exchange by trichloroethylene and its metabolites. Toxicol. Eur. Res.1981, 3(2):63-67.
34. Seiji K, Jin C, Watanabe T, et al. Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene, trichloroethylene, or tetrachloroethylene, with reference to smoking habits. Int. Arch. Occup. Environ. Health 1990, 62(2):171-176.
35. Nagaya T, Ishikawa N, Hata H. Sister-chromatid exchanges in lymphocytes of workers exposed to trichloroethylene. Mutat. Res. 1989, 222(3):279-382.
36. Kautiainen A, Vogel JS, Turteltaub KW. Dose-dependent binding of trichloroethylene to hepatic DNA and protein at low doses in mice. Chem. Biol. Interact, 1997,106(2):109-121.
37. Halmes NC, Perkins EJ, McMillan DC, et al. Detection of trichloroethylene- protein adducts in rat liver and plasma. Toxicol. Lett.1997, 92(3):187-194.
38. Elfarra AA, Krause RJ, Last AR, et al. Species- and sex-related differences in metabolism of trichloroethylene to yield chloral and trichloroethanol in mouse, rat, and human liver microsomes. Drug Metab. Dispos.1998, 26(8):779-785.
39. Nakajima T, Kamijo Y, Usuda N, at al. Sex-dependent regulation of hepatic peroxisome proliferation in mice by trichloroethylene via peroxisome proliferator-activated receptor alpha (PPARalpha). Carcinogenesis.2000 21(4): 677-682.
40. Cummings BS, Lash H. Metabolism and toxicity of trichloroethylene and S-(1,2-dichloroviny1)-L-cysteine in freshly isolated human proximal tubular cells. Toxicol Sci. 2000, 53(2):458-466.
41. Cummings BS, Lasker JM, Lash LH. Expression of glutathione-dependent enzymes and cytochrome P450s in freshly isolated and primary cultures of proximal tubular cells from human kidney. J. Pharmacol. Exp. Ther. 2000, 293 (2):677-685.
42. Snawder JE, Lipscomb JC. Interindividual variance of cytochrome P450 forms in human hepatic microsomes: correlation of individual forms with xenobiotic metabolism and implications in risk assessment. Regul. Toxicol. Pharmacol. 2000, 32 (2):200-209.
43. Kato Y, Asano Y, Cooper AJ. Inactivation of brain and kidney aspartate aminotranslerases by S-(1,2-dichlorovinyl)-L-cysteine and by S-(1,1,2,2,-tetrafluoroethyl)-L-cysteine . Dev . Neurosci. 1996, 18 (5-6):505-514.
44. Cummings BS, Parker JC, Lash LH. Role of cytochrome P450 glutathione S-transferase alpha in the metabolism and cytotoxicity of trichloroethylene in rat kidney. Biochem. Pharmacol. 2000, 59 (5):531-543.
45. Cummings BS, Lash LH. Cytochrome P450-Dependent Metabolism of Trichloroethylene in Rat kidney. Toxicol. Sci. 2001, 60(1):11-19.
46. Green T. Pulmonary toxicity and carcinogenicity of trichloroethy-lene: Species differences and modes of action. Environ. Health Perspect. 2000,108 (Suppl 2): 261-264.
47. Bull RJ. Mode of action of liver tumor induction trichloroethylene and its metabolites, trichloroacetate and dichloroacetate. Environ. Health Perspect. 2000,108(Suppl 2):241-259.
48. Atkinson A, Meeks RG, Roy D. Increased oxidative stress in the liver of mice treated with trichloroethylene. Biochem. Mol. Biol. Int.1993, 31(2):297-304.
49. Steel GL, Pravecek TL, Carmichael AJ. Trichloroethylene metabolism in vitro: an CPR/SPI N trapping study. Hum. Exp. Toxicol.1996, 15(11): 878-884.
50.张锦周,黄海雄,庄志雄,等.三氯乙烯急性染毒对大鼠肝脂质过氧化的影响.中国公共卫生. 2000, 16(4):308-309.
51. Watanabe S, Fukui T. Suppressive effect of curcumin on trichloroethylene-Induced oxidative stress. J. Nutr. Sci. Vitaminol. 2000, 46 (5):230-234.
52.杨翠婵,李伯灵,邹志方.低剂量三氯乙烯对作业工人脂质过氧化作用的影响.华南预防医学. 2002, 28(3):23-24.
53.黄锦生,陈惠珍,吴平方,等.低浓度三氯乙烯对人体抗氧化物酶系统影响.中国公共卫生. 2002, 18(3):282-283.
54.方城.过氧化酶体与致癌的关系.国外医学卫生学分册. 2000, 27 (5):289-292
55. Klaunig JE, Babieh MA, Baetcke KP, et a1. PPARαagonist-induced rodent tumors: modes of action and human relevance. Crit. Rev. Toxicol. 2003, 33(6):655-780.
56. Dzhekova-Stojkova S, Bogdanska J, Stojkova Z. Peroxisome p roliferators: their biological and toxicological effects. Clin. Chem. Lab. Med. 2001, 39(6): 468-474.
57. Tao L, Ge R, Xie M, et al. Effect of trichloroethylene on DNA methylation and expression of early-intermediate protooncogenes in the liver of B6C3F1 mice. J Biochem. Mol. Toxicol. 1999, 13 (5):231-237.
58. Tao L,Yang S,Xie M,et al. Effect of trichloroethylene and its metabolites, dichloroacetic acid and trichloroacetic acid, on the methylation and expression of c-jun and c-myc protooncogenes in mouse liver: prevention by methionirne. Toxicol. Sci. 2000, 54 (2):399-407.
59. Tao L, Kramer PM, Ge R, et al. Effect of dichloroacetic acid and trichloroacetic acid on DNA methylation in liver and tumors of female B6C3F1 mice. Toxicol. Sci. 1998, 43 (2):139-144.
60. Bruning T, Bolt HM. Renal toxicity and carcinogenicity of trichloroethylene: key results,mechanisms,and controversies. Crit. Rev. Toxicol. 2000,30 (3):253-285
61. Schraml P, Zhaou M, Richter J. Analysis of kidney tumors in trichloroethylene exposed workers by comparative genomic hybridzation and DNA sequence analysis. Verh. Dtsch. Ges. Pathol. 1999,83:218-224.
62. Moore MM, Harrington BK. Mutagenicity of trichloroethylene and its metabolites: implications for the risk assessment of triehloroethylene. Environ. Health Perspect. 2000, 108(Suppl 2):215-223.
63. Lash LH, Parker JC, Modes of action of trichloroethylene for kidney tumorigenesis. Environ. Health Perspect. 2000, 108(Suppl 2):225-240.