Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.
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.
D001580:Benzopyrenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D004988:Ethers, Cyclic / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D011721:Pyrenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001580:Benzopyrenes; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D011721:Pyrenes; C027599:cyclopenta(cd)pyrene 3,4-oxide