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Induction of specific frameshift and base substiution events by benzo[a]pyrene diol expoxide in excision-repair-deficient Escherichia coli
Department of Biology,York University 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada
2To whom correspondence should be addressed
We have determined the DNA alterations recovered after treatment with (±)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,l0- tetrahydrobenzo [a]pyrene [(±)-anti-BPDE] in the lacl 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 dupil rations, were also moderately induced. The great majority of -(G:C) frameshifis, 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 sub stitution mutagenesis In E.coli proceeds through abasic in tennedlates across from which adenine is preferentially incorporated during replication.
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