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用氯代烃的半胱氨酸 S-共轭物处理叙利亚仓鼠胚胎成纤维细胞后非定标性 DNA 合成及微核形成的诱导作用

Induction of unscheduled DNA synthesis and micronucleus formation in Syrian hamster embryo fibroblasts treated with cysteine S-conjugates of chlorinated hydrocarbons.

作者信息

Vamvakas S, Dekant W, Schiffmann D, Henschler D

机构信息

Institut für Toxikologie, Universität Würzburg, Federal Republic of Germany.

出版信息

Cell Biol Toxicol. 1988 Dec;4(4):393-403. doi: 10.1007/BF00117768.

Abstract

S-(chloroethyl)-cysteine (CEC) and S-(1,2-dichlorovinyl)-cysteine (DCVC) have been proposed as intermediates in the metabolic transformation of the carcinogens 1,2-dichloroethane and 1,1,2-trichloroethylene. We have tested the ability of CEC and DCVC to induce DNA repair and genotoxic effects at the chromosomal level by comparative assessment of unscheduled DNA synthesis induction and micronucleus formation in Syrian hamster embryo fibroblasts. CEC induced a potent and dose-dependent response in both assays, whereas DCVC treatment resulted in a comparatively weak induction of DNA repair and failed to raise micronucleus formation above control rates. Inhibition of cysteine conjugate beta-lyase diminished the effect of DCVC, but had no influence on the genotoxicity of CEC either in the unscheduled DNA synthesis or micronucleus assay.

摘要

S-(氯乙基)-半胱氨酸(CEC)和S-(1,2-二氯乙烯基)-半胱氨酸(DCVC)被认为是致癌物1,2-二氯乙烷和1,1,2-三氯乙烯代谢转化过程中的中间体。我们通过比较评估叙利亚仓鼠胚胎成纤维细胞中DNA合成的非预定诱导和微核形成,测试了CEC和DCVC在染色体水平诱导DNA修复和遗传毒性效应的能力。在这两种试验中,CEC均诱导出强烈的剂量依赖性反应,而DCVC处理导致DNA修复的诱导相对较弱,且未能使微核形成率高于对照水平。半胱氨酸共轭β-裂解酶的抑制减弱了DCVC的作用,但在非预定DNA合成或微核试验中对CEC的遗传毒性均无影响。

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