苯并[a]芘和环戊[cd]芘的致癌环氧化物通过特定的颠换诱导碱基置换。
Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.
作者信息
Eisenstadt E, Warren A J, Porter J, Atkins D, Miller J H
出版信息
Proc Natl Acad Sci U S A. 1982 Mar;79(6):1945-9. doi: 10.1073/pnas.79.6.1945.
Abstract
We have determined the spectrum of base-pair substitution mutations induced in the lacI gene of a uvrB- strain of Escherichia coli by two polycyclic aromatic hydrocarbons--(+/-)7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BPDE), and 3,4-epoxycylopenta[cd]pyrene (CPPE). Approximately 10% of all lacI mutations induced by either BPDE or CPPE are nonsense mutations, suggesting that base-pair substitutions are a large fraction of the mutational events induced by these agents in the uvrB- bacteria. Both carcinogens specifically induced the G . C leads to T . A and, to a lesser extent, the A . T leads to T . A transversions. One possible mechanism for transversion induction at G . C sites by BPDE might involve carcinogen binding to the exocyclic amino group of guanine in the template strand followed by a rotation of the modified base around its glycosylic bond from the anti to the syn conformation. This could allow specific pairing of modified bases with an imino tautomer of adenine.
摘要
我们已经确定了两种多环芳烃——（±）7α，8β-二羟基-9β，10β-环氧-7，8，9，10-四氢苯并[a]芘（BPDE）和3，4-环氧环戊[cd]芘（CPPE）在大肠杆菌uvrB-菌株的lacI基因中诱导产生的碱基对替换突变谱。由BPDE或CPPE诱导的所有lacI突变中约10%为无义突变，这表明碱基对替换是这些试剂在uvrB-细菌中诱导的大部分突变事件。两种致癌物都特异性地诱导了G.C突变为T.A，并且在较小程度上诱导了A.T突变为T.A颠换。BPDE在G.C位点诱导颠换的一种可能机制可能涉及致癌物与模板链中鸟嘌呤的环外氨基结合，随后修饰碱基围绕其糖苷键从反式构象旋转到顺式构象。这可能允许修饰碱基与腺嘌呤的亚氨基互变异构体进行特异性配对。
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