MUTAGENICITY OF QUINONES - PATHWAYS OF METABOLIC-ACTIVATION AND DETOXIFICATION
MUTAGENICITY OF QUINONES - PATHWAYS OF METABOLIC-ACTIVATION AND DETOXIFICATION
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DOI：
10.1073/pnas.81.6.1696
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
AMES, BN
中科院分区：
文献类型：
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作者：
CHESIS, PL;LEVIN, DE;AMES, BN
广泛分布于自然界的醌类化合物在沙门氏菌TA104试验菌株中表现出致突变性。详细研究了甲萘醌、苯并[a]芘3,6-醌、9,10-菲醌和丹蒽醌4种醌类化合物在本试验体系中致突变性的代谢途径和解毒途径。NAD(P) h -醌氧化还原酶（DT-diaphorase）催化的2电子还原不具有致突变性，而nadph -细胞色素P-450还原酶催化的1电子还原则具有致突变性，但丹红仅具有轻微致突变性。通过这一途径发现醌类化合物的致突变性可归因于氧自由基的产生。细胞色素P-450单加氧酶也在这些醌的解毒和生物活化中发挥了重要作用。在细胞色素p -450依赖性反应中，菲蒽醌转化为非诱变代谢物，而丹红则转化为高度诱变代谢物。这些研究显示了醌类化合物致突变性中代谢途径的复杂性。
The mutagenicity of various quinones, a class of compounds widely distributed in nature, is demonstrated in the Salmonella TA104 tester strain. The metabolic pathways by which 4 quinones, menadione, benzo[a]pyrene 3,6-quinone, 9,10-phenanthrenequinone and danthron, caused mutagenicity in this test system were investigated in detail as were the detoxification pathways. The 2-electron reduction of these quinones by NAD(P)H-quinone oxidoreductase (DT-diaphorase) was not mutagenic, whereas the 1-electron reduction, catalyzed by NADPH-cytochrome P-450 reductase, was mutagenic, except for danthron, which was only slightly mutagenic. The mutagenicity of the quinones via this pathway was found to be attributable to the generation of oxygen radicals. The cytochrome P-450 monooxygenase also played a significant role in the detoxification and bioactivation of these quinones. Phenanthrenequinone was converted to a nonmutagenic metabolite in a cytochrome P-450-dependent reaction, whereas danthron was converted to a highly mutagenic metabolite. These studies show the complexity of metabolic pathways involved in the mutagenicity of quinones.