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大鼠肝脏中5-硝基苊经C-羟基化和硝基还原形成的诱变代谢产物的鉴定。

Identification of mutagenic metabolites formed by C-hydroxylation and nitroreduction of 5-nitroacenaphthene in rat liver.

作者信息

EL-Bayoumy K, Hecht S S

出版信息

Cancer Res. 1982 Apr;42(4):1243-8.

PMID:7060001
Abstract

The metabolism of the mutagen and carcinogen, 5-nitroacenaphthene, by the 9000 x g supernatant from the livers of Aroclor-pretreated rats was studied. The major primary metabolites were 1-hydroxy-5-nitroacenaphthene and 2-hydroxy-5-nitroacenaphthene. These metabolites were oxidized to 1-oxo-5-nitroacenaphthene and 2-oxo-5-nitroacenaphthene, hydroxylated to cis-1,2-dihydroxy-5-nitroacenaphthene and trans-1,2-dihydroxy-5-nitroacenaphthene, and reduced to 1-hydroxy-5-aminoacenaphthene and 2-hydroxy-5-aminoacenaphthene. Reduction of 1- and 2-oxo-5-nitroacenaphthene to 1-oxo- and 2-oxo-5-aminoacenaphthene was also observed. When incubations were carried out in a N2-enriched atmosphere (10% O2 in N2), the major metabolites were 1-hydroxy- and 2-hydroxy-5-nitroacenaphthene and 2-oxo-5-aminoacenaphthene. Selected metabolites were tested for mutagenicity toward Salmonella typhimurium TA 98. The most mutagenic of the metabolites tested, in the presence or absence of rat liver 9000 x g supernatant, were 1-hydroxy-5-nitroacenaphthene and 1-oxo-5-nitroacenaphthene. These results indicate that the 9000 x g supernatant from the livers of Aroclor-pretreated rats is capable of catalyzing both the oxidation and reduction of 5-nitroacenaphthene and that the reduced derivatives of 1-hydroxy- or 2-hydroxy- or 1-oxo- or 2-oxo-5-nitroacenaphthene are proximate mutagens.

摘要

研究了经多氯联苯预处理的大鼠肝脏9000×g上清液对诱变剂和致癌物5-硝基苊的代谢情况。主要的初级代谢产物是1-羟基-5-硝基苊和2-羟基-5-硝基苊。这些代谢产物被氧化为1-氧代-5-硝基苊和2-氧代-5-硝基苊,羟基化为顺式-1,2-二羟基-5-硝基苊和反式-1,2-二羟基-5-硝基苊,并还原为1-羟基-5-氨基苊和2-羟基-5-氨基苊。还观察到1-和2-氧代-5-硝基苊还原为1-氧代-和2-氧代-5-氨基苊。当在富氮气氛(氮气中含10%氧气)中进行孵育时,主要代谢产物是1-羟基-和2-羟基-5-硝基苊以及2-氧代-5-氨基苊。对选定的代谢产物进行了对鼠伤寒沙门氏菌TA 98的致突变性测试。在所测试的代谢产物中,无论有无大鼠肝脏9000×g上清液存在,最具致突变性的是1-羟基-5-硝基苊和1-氧代-5-硝基苊。这些结果表明,经多氯联苯预处理的大鼠肝脏9000×g上清液能够催化5-硝基苊的氧化和还原,并且1-羟基-或2-羟基-或1-氧代-或2-氧代-5-硝基苊的还原衍生物是直接诱变剂。

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