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苯乙烯的代谢与遗传毒性。

Metabolism and genotoxicity of styrene.

作者信息

Vainio H, Norppa H, Hemminki K, Sorsa M

出版信息

Adv Exp Med Biol. 1981;136 Pt A:257-74. doi: 10.1007/978-1-4757-0674-1_15.

Abstract

An overview on the metabolism and genotoxicity of styrene is given in this article. The mutagenic potency of styrene has been confirmed in a number of test systems providing the metabolic activation of styrene. Styrene is converted to styrene-7,8-oxide as catalyzed by cytochrome P-450 cored enzyme complex. Styrene-7,8-oxide is mutagenic in prokaryotic and eukaryotic test systems without metabolic activation. It reacts with nucleic acid bases, especially with deoxyguanosine producing 7-alkylguanine and deoxycytidine producing N-3 alkylcytosine. Quite recently, styrene-7,8-oxide has been found to be a potent carcinogen in rats. In human whole blood cultures, styrene is metabolized into styrene-7,8-oxide. Styrene is able to induce both SCEs and chromosomal aberrations in cultured lymphocytes. The clastogenic action of styrene can be explained by the metabolism of styrene into styrene-7,8-oxide in cultured human blood cells. Although also an arene oxide, styrene-3,4-oxide, has been suggested in the biotransformation of styrene, the evidence so far supports the view that the vinyl group oxidation and oxirane formation plays a predominant role in the genotoxicity of styrene.

摘要

本文对苯乙烯的代谢和遗传毒性进行了综述。在一些能提供苯乙烯代谢活化作用的测试系统中,已证实苯乙烯具有诱变效力。苯乙烯在细胞色素P - 450核心酶复合物的催化下转化为苯乙烯 - 7,8 - 氧化物。苯乙烯 - 7,8 - 氧化物在无代谢活化的原核和真核测试系统中具有致突变性。它与核酸碱基反应,特别是与脱氧鸟苷反应生成7 - 烷基鸟嘌呤,与脱氧胞苷反应生成N - 3烷基胞嘧啶。最近,已发现苯乙烯 - 7,8 - 氧化物在大鼠中是一种强效致癌物。在人全血培养中,苯乙烯代谢为苯乙烯 - 7,8 - 氧化物。苯乙烯能够在培养的淋巴细胞中诱导姐妹染色单体交换(SCEs)和染色体畸变。苯乙烯的致断裂作用可以通过苯乙烯在培养的人血细胞中代谢为苯乙烯 - 7,8 - 氧化物来解释。虽然也有人提出苯乙烯 - 3,4 - 氧化物作为苯乙烯生物转化中的一种环氧芳烃,但目前的证据支持这样的观点,即乙烯基氧化和环氧乙烷形成在苯乙烯的遗传毒性中起主要作用。

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