Induction of specific frameshift and base substitution events by benzo[a]pyrene diol epoxide in excision-repair-deficient Escherichia coli.
We have determined the DNA alterations recovered after treatment with (+-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+-)-anti-BPDE] in the lacI gene of excision-repair-deficient (Uvr-) Escherichia coli. The high induction of -(G:C) frameshifts, G:C----T:A and A:T----T:A transversions, and the presence of complex mutations of a particular motif, distinguish the mutational distribution recovered in the Uvr- strain, although other mutational classes, including -(A:T) frameshifts and duplications, were also moderately induced. The great majority of -(G:C) frameshifts, the predominant mutation recovered, occurred in runs of G residues. The G:C----T:A transversion was found to occur more frequently (10/12 occurrences) at 5'-Y-G-3' sites, sequences at which the labile BPDE:N7G adduct has been predicted to occur. Moreover, the relative proportions of G:C----T:A, A:T----T:A and G:C----A:T mutations correlate well with the expected proportions of alkali-labile lesions at G, A and C residues. These results support the model that (+-)-anti-BPDE-induced base substitution mutagenesis in E.coli proceeds through abasic intermediates across from which adenine is preferentially incorporated during replication.
Bernelot-Moens
C
C
Department of Biology, York University, Toronto, Ontario, Canada.
Glickman
B W
BW
Gordon
A J
AJ
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000225:Adenine / Q000502:physiology; D001482:Base Composition; D001483:Base Sequence; D003596:Cytosine / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics*; D004101:Dihydroxydihydrobenzopyrenes / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics*; D006147:Guanine / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D013941:Thymine / Q000502:physiology
D004269:DNA, Bacterial; D004101:Dihydroxydihydrobenzopyrenes; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine