Metabolism of benzo[f]quinoline by rat liver microsomes.
Metabolism of benzo[f]quinoline by rat liver microsomes.
复制标题
大鼠肝微粒体对苯并[f]喹啉的代谢。
DOI：
10.1093/carcin/8.12.1861
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发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Sikka,HC
中科院分区：
文献类型：
--
作者：
Kandaswami,C;Kumar,S;Dubey,SK;Sikka,HC
The metabolism of [1,3-14C]benzo[f]quinoline (BfQ) by liver microsomes from control, 3-methylcholanthrene (3-MC)-pretreated and phenobarbital (PB)-pretreated rats has been investigated in order to gain insights into the effect of mixed function oxidase inducers on the types and levels of specific metabolites as formedin vitro. The rates of metabolism of BfQ by liver microsomes from control, 3-MC- and PB-pretreated rats were 0.5, 3.6 and 2.4 nmol/min/mg of respectively. The most predominant metabolite of BfQ detected with liver microsomes from 3-MC-pretreated rats was BfQ-7,8-dihydrodiol, a precursor of the bay-region diol epoxide, constituting 41% of the total ethyl acetate-extractable metabolites. Other metabolites obtained along with their relative proportions were as follows: BfQ-N-oxide, 23% 7-hydroxyBfQ, 15%; 9-hydroxyBfQ, 9%; and BfQ-9,10-dihydrodiol, 6%. BfQ-5,6- dihydrodiol, a K-region dihydrodiol, was a trace metabolite representing ˜1.0% of the total metabolism. Liver microsomes from PB-pretreated rats oxidized BfQ primarily to BfQ-N-oxide and 9-hydroxyBfQ, which constituted 41% and 20% of the total ethyl acetate-extractable metabolites of BfQ. The relative proportions of BfQ-9,10-dihydrodiol, BfQ-7,8-dihydrodiol and 7-hydroxy-BfQ formed were 12%, 3% and 13% respectively, while the figure for BfQ-5,6-dihydrodiol was 0.5%. The profile of metabolites formed by liver microsomes from control rats was similar to that generated by microsomes from PB-pretreated rats. While benzo-ring metabolites represented a major part of the metabolism of BfQ by liver microsomes from either 3-MC- or PB-pretreated rats, these two types of microsomes exhibited a positional selectivity in the oxidation of BfQ, the former primarily attacking the 7,8-position of BfQ while the latter preferentially oxidizing the 9,10-position. The preponderance of the potentially mutagenic BfQ-7,8-dihydrodiol amongst the metabolites generated by liver microsomes from 3-MC-pretreated rats suggests a possible role for cytochrome P-450c, the major form of rat hepatic cytochrome P-450 induced by 3-MC, in the metabolic activation of BfQ.
