Mutational Consequences on Replication of M13 Constructs Containing Isomeric Diol Epoxide Adducts in E. coli

Eight isomeric dGuo and eight dAdo adducts resulting from cis and trans opening of each of the four optic-ally active diol epoxides (DEs) derived from benzo[a]pyrene (BaP) and benzo[c]phenanthrene (BcPh) were placed in each of two 16-mer DNA sequences to give 32 modified oligonucleotides, which were ligated into M13mp7L2 and allowed to replicate in SOS-induced Escherichia coli. The effects of parent hydrocarbon, adduct stereochemistry, and sequence context on mutagenic response are highly interdependent. BaP DE adducts are generally more mutagenic than the corresponding BcPh adducts. The mutational frequency is generally larger for cis- relative to trans-opened DE adducts of both dGuo and dAdo. In a similar toTA*Gsimilar to context, BcPh DE dAdo adducts (A*) with R configuration at the site of attachment to the adenine base produced very few substitution mutations when compared with adducts having S configuration. This configurational effect is not observed for BaP DE dAdo adducts, nor for BaP or BcPh dGuo adducts.