Induction of specific frameshift and base substiution events by benzo[a]pyrene diol expoxide in excision-repair-deficient Escherichia coli

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Abstract
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.