EXCEPTIONAL MUTAGENICITY OF A BENZO[ALPHA]PYRENE DIOL EPOXIDE IN CULTURED MAMMALIAN-CELLS
EXCEPTIONAL MUTAGENICITY OF A BENZO[ALPHA]PYRENE DIOL EPOXIDE IN CULTURED MAMMALIAN-CELLS
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DOI：
10.1038/261052a0
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发表时间：
1976-01-01
期刊：
影响因子：
64.8
通讯作者：
BROOKES, P
中科院分区：
文献类型：
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作者：
NEWBOLD, RF;BROOKES, P
苯并[a]芘(BP)是一类化学惰性的致癌物，为了发挥其细胞毒性、致突变和致癌作用，需要通过混合功能加氧酶(MFC)代谢激活能够与细胞大分子1-3发生共价反应的产物。更具体地说，在小鼠皮肤4和各种培养的哺乳动物细胞5中已经表明，在DNA的情况下，这种反应的程度与化合物的致癌活性有关。DNA是这一系列碳氢化合物的重要靶标的假设进一步得到了证据的支持，即最具致癌性的成员对体外培养的仓鼠细胞也是最具诱变性的。在这里，我们提出证据表明，BP的二醇环氧化物衍生物在应用于哺乳动物细胞时是一种强大的诱变剂，因此该化合物是BP的最终致癌代谢物。
BENZO[a]PYRENE (BP) is one of a group of chemically inert carcinogens which, in order to exert their cytotoxic, mutagenic and carcinogenic effects, require metabolic activation by mixed function oxygenases (MFC) to products capable of covalent reaction with cellular macromolecules1–3. More specifically, it has been shown in mouse skin4and various cultured mammalian cells5, that, in the case of DNA, the extent of this reaction correlates with the carcinogenic potency of the compound. The hypothesis that DNA is the important target for this series of hydrocarbons is further supported by evidence that the most carcinogenic members are also the most mutagenic towards hamster cellsin vitro1. Here we present evidence that a diol epoxide derivative of BP is a powerful mutagen when applied to mammalian cells, and suggest therefore that this compound is the ultimate carcinogenic metabolite of BP.