MUTAGENIC POTENTIAL OF STEREOISOMERIC BAY-REGION (-CIS-ANTI-BENZO[A]PYRENE AND (-)-CIS-ANTI-BENZO[A]PYRENE DIOL EPOXIDE-N-2-2'-DEOXYGUANOSINE ADDUCTS IN ESCHERICHIA-COLI AND SIMIAN KIDNEY-CELLS())

We have investigated the mutagenic potential of site-specifically posi tioned DNA adducts with (+)- and (-)-cis-anti stereochemistry derived from the binding of r7, t8-dihydroxy-t9, 10-epoxy-7,8,9,10-tetrahydrob enzo[a]pyrene (BPDE) to N-2-2'-deoxyguanosine (G(1) or G(2)) in the se quence context (5')TCCTCCTG(1) G(2)CCTCTC. BPDE-modified oligodeoxynuc leotides were ligated to a single-stranded DNA vector and replicated i n Escherichia coli or simian kidney (COS7) cells. The presence of (+)- or (-)-cis adduct strongly reduced the yield of transformants in E. c oli, and the yield was improved by the induction of SOS functions. Bot h adducts were mutagenic in E. coli and COS cells, generating primaril y G --> T transversions. In E, coli, the (-)-cis adduct was more mutag enic than the (+)-cis adduct, while in COS cells, both adducts were eq ually mutagenic. These results were compared with those obtained with stereoisomeric (+)- and (-)-trans adducts [Moriya, M., et al. (1996) B iochemistry 35, 16646-16651). In E, coli, cis adducts, especially (-)- cis adducts, are consistently more mutagenic than the comparable trans adduct, In COS cells, trans adducts yield higher frequencies of mutat ions than the two cis adducts and, with the exception of the high-muta tion frequency associated with the (+)-trans adduct at G(2), relativel y small differences in mutation frequencies are observed for the three other adducts. In E. coli, mutation frequency is a pronounced functio n of adduct stereochemistry and adduct position. These findings sugges t that the fidelity of translesional synthesis across BPDE-dG adducts is strongly influenced by adduct stereochemistry, nucleotide sequence context, and the DNA replication complex.