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

Abstract

Eight isomeric dGuo and eight dAdo adducts resulting from cis and trans opening of each of the four optically active diol epoxides (DEs) derived from benzo[ a ]pyrene (B a P) and benzo[ c ]phenanthrene (B c Ph) 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. B a P DE adducts are generally more mutagenic than the corresponding B c Ph adducts. The mutational frequency is generally larger for cis - relative to trans -opened DE adducts of both dGuo and dAdo. In a ∼TA*G∼ context, B c Ph 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 B a P DE dAdo adducts, nor for B a P or B c Ph dGuo adducts.