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氯乙烯对细胞色素P - 450及肝脏混合功能氧化酶系统其他组分的失活作用:一项体内研究。

Vinyl chloride-induced deactivation of cytochrome P-450 and other components of the liver mixed function oxidase system: an in vivo study.

作者信息

Reynolds E S, Moslen M T, Szabo S, Jaeger R J

出版信息

Res Commun Chem Pathol Pharmacol. 1975 Dec;12(4):685-94.

PMID:175418
Abstract

Liver microsomal enzyme activities were measured 24 hr after a 6 hr exposure to 5% vinyl chloride in male rats pretreated with phenobarbital, Aroclor 1254 or the control vehicle. Liver injury as indicated by serum transaminase elevations after vinyl chloride, was found only in phenobarbital and Aroclor 1254 animals while cytochrome P-450 contents and oxidative N-demethylation of aminoantipyrine and ethylmorphine were markedly decreased in all groups. Glucose-6-phosphatase, cytochrome b5 and NADPH and NADH cytochrome P-450 reductase were scarcely affected. This selective enzymatic deactivation is consistent with a cytochrome P-450 centered activation of vinyl chloride to a reactive electrophile.

摘要

在用苯巴比妥、多氯联苯混合物1254或对照赋形剂预处理的雄性大鼠中,暴露于5%氯乙烯6小时后24小时测量肝脏微粒体酶活性。氯乙烯暴露后血清转氨酶升高所表明的肝损伤仅在苯巴比妥和多氯联苯混合物1254处理的动物中发现,而所有组中细胞色素P-450含量以及氨基安替比林和乙基吗啡的氧化N-脱甲基作用均显著降低。葡萄糖-6-磷酸酶、细胞色素b5以及NADPH和NADH细胞色素P-450还原酶几乎未受影响。这种选择性酶失活与以细胞色素P-450为中心的氯乙烯激活为活性亲电试剂相一致。

相似文献

1
Vinyl chloride-induced deactivation of cytochrome P-450 and other components of the liver mixed function oxidase system: an in vivo study.氯乙烯对细胞色素P - 450及肝脏混合功能氧化酶系统其他组分的失活作用:一项体内研究。
Res Commun Chem Pathol Pharmacol. 1975 Dec;12(4):685-94.
2
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引用本文的文献

1
Monooxygenase activity and ultrastructural changes of liver in the course of chronic exposure of rats to vinyl chloride.大鼠长期接触氯乙烯过程中肝脏的单加氧酶活性及超微结构变化
Int Arch Occup Environ Health. 1980;46(3):241-9. doi: 10.1007/BF00380014.
2
Computer-assisted mechanistic structure-activity studies: application to diverse classes of chemical carcinogens.计算机辅助的机理结构-活性研究:应用于各类化学致癌物
Environ Health Perspect. 1985 Sep;61:69-96. doi: 10.1289/ehp.856169.
3
Damage to hepatic cellular membranes by chlorinated olefins with emphasis on synergism and antagonism.
氯化烯烃对肝细胞膜的损伤,重点在于协同作用和拮抗作用。
Environ Health Perspect. 1977 Dec;21:137-47. doi: 10.1289/ehp.7721137.
4
Environmental aspects of injury and disease: liver and bile ducts.损伤与疾病的环境因素:肝脏和胆管
Environ Health Perspect. 1977 Oct;20:1-13. doi: 10.1289/ehp.77201.
5
Mutagenic and alkylating metabolites of halo-ethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver tissues. Evidence for oxirane formation by P450-linked microsomal mono-oxygenases.啮齿动物或人类肝脏组织产生的卤代乙烯、氯丁二烯和二氯丁烯的诱变和烷基化代谢产物。细胞色素P450相关微粒体单加氧酶形成环氧乙烷的证据。
Arch Toxicol. 1979 Feb 23;41(4):249-77. doi: 10.1007/BF00296896.