苯并[a]芘7,8-二氢二醇在新生小鼠中比苯并[a]芘更致癌,Nature

当前位置： X-MOL 学术 › Nature › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

苯并[a]芘7,8-二氢二醇在新生小鼠中比苯并[a]芘更致癌
Nature ( IF 50.5 ) Pub Date : 1977-03-01 , DOI: 10.1038/266378a0
JAIME KAPITULNIK , WAYNE LEVIN , ALLAN H. CONNEY , HARUHIKO YAGI , DONALD M. JERINA

James 和 Elizabeth Miller 的开创性研究将许多化学物质的致癌作用与这些化合物代谢为与关键细胞成分结合的反应性中间体 1,2 相关联，导致对这些反应性代谢物（最终致癌物）的性质和化学结构的研究和它们的代谢前体（近端致癌物）。环境致癌物苯并 [a] 芘 (BP) 被微粒体酶代谢为芳烃氧化物、苯酚和二氢二醇。BP 代谢物 (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) 通过肝微粒体的代谢激活导致与 DNA 的结合比代谢激活更多BP（参考文献 3）。参与与 DNA 结合的反应性代谢物是 trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro BP (BP 7,8-diol-9, 10-环氧化物）（参考文献 4）。这种二醇环氧化物的两种立体异构体是由 BP 7,8-二氢二醇（参考文献 5-8）酶促形成的，对细菌和哺乳动物细胞具有高度诱变性 9-15，表明 BP 7,8-二醇-9,10-环氧化物可能是 BP 的最终致癌代谢物。我们在此报告，与苯并 [a] 芘相比，对新生小鼠施用 BP 7,8-二氢二醇会导致更多的恶性淋巴瘤和肺腺瘤。这是首次证明多环芳烃代谢物比母体化合物致癌性更强。一种立体异构 BP 7,8-diol-9,10-epoxides ((±)-trans-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydro BP; diol epoxide-2 ；也称为二醇环氧化物 I（参考文献 11）或反异构体（参考文献 11）。

"点击查看英文标题和摘要"

Benzo[a]pyrene 7,8-dihydrodiol is more carcinogenic than benzo[a]pyrene in newborn mice

THE pioneering research by James and Elizabeth Miller relating the carcinogenic effects of many chemicals to the metabolism of these compounds to reactive intermediates which bind to critical cellular compoenents1,2 led to studies of the nature and chemical structure of these reactive metabolites (ultimate carcinogens) and their metabolic precursors (proximate carcinogens). The environmental carcinogen benzo[a]pyrene (BP) is metabolised by microsomal enzymes to arene oxides, phenols and dihydrodiols. Metabolic activation of the BP metabolite (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) by liver microsomes resulted in more binding to DNA than did the metabolic activation of BP (ref. 3). The reactive metabolite involved in the binding to DNA was a trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro BP (BP 7,8-diol-9,10-epoxide) (ref. 4). Both stereoisomers of this diol epoxide, which are enzymatically formed from BP 7,8-dihydrodiol (refs 5–8), were highly mutagenic to bacterial and mammalian cells9–15 suggesting that a BP 7,8-diol-9,10-epoxide might be an ultimate carcinogenic metabolite of BP. We report here that administration of BP 7,8-dihydrodiol to newborn mice caused more malignant lymphomas and pulmonary adenomas than did administration of benzo[a]pyrene. This is the first demonstration of a metabolite of a polycyclic aromatic hydrocarbon that is more carcinogenic than the parent compound. One of the stereoisomeric BP 7,8-diol-9,10-epoxides ((±)-trans-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydro BP; diol epoxide-2; also termed diol epoxide I (ref. 11) or anti-isomer (ref. 16)) produced about the same number of pulmonary adenomas as a 50-fold higher dose of BP.

更新日期：1977-03-01

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南