MUTAGENIC ACTIVITY OF THE 4,5-DIHYDRODIOLS AND 9,10-DIHYDRODIOLS OF BENZOI!FLUORANTHENE AND THEIR SYN-DIHYDRODIOL AND ANTI-DIHYDRODIOL EPOXIDES IN SALMONELLA-TYPHIMURIUM

The objective of this study was to determine the relative mutagenic ac tivities of the major dihydrodiol metabolites of benzoi!fluoranthene (Bi!F) and their corresponding syn- and anti-dihydrodiol epoxides. Sa lmonella typhimurium tester strains TA97a, TA98, and TA100 were used t o evaluate the mutagenic potencies of the parent hydrocarbon and these suspect proximate and ultimate mutagenic metabolites. Bi!F and the t rans-dihydrodiol metabolites were active only in the presence of an ex ternal metabolic activation system (S9) with the exception of the Bi! F-4,5-diol, which was weakly active in TA98 and TA100 in the absence o f S9. The Bi!F-4,5-diol was more mutagenic than the Bi!F-9,10-diol i n tester strains TA98 and TA100, whereas the opposite effect was obser ved in TA97a. In the absence of S9, the anti-Bi!F-4,5-diol epoxide wa s more mutagenic than the Syn-Bi!F-4,5-diol epoxide and the syn- and anti-Bi!F-9,10-diol epoxides in tester strains TA97a and TA100. The e xceptional mutagenic potency of the anti-Bi!F-4,5-diol epoxide in TA1 00 resembles that observed by epoxides located within a fjord,or by th e anti-diol epoxides of bay region methylated polycyclic aromatic hydr ocarbons. In contrast, the mutagenicity of the pseudo bay region dihyd rodiol epoxides arising from the Bi!F-9, 1 0-diol more closely resemb les that observed with the classical bay region dihydrodiol epoxides o f chrysene. In summary, both dihydrodiol metabolites of Bi!F are muta genic in S. typhimurium, and the relative potency varies among the tes ter strains. The highest mutagenic response was achieved in tester str ain TA100, which detects base-pair substitutions. The most potent dire ct-acting dihydrodiol epoxide in this tester strain was the anti-Bi!F -4,5-diol epoxide, which agrees with the results of mouse skin paintin g studies that indicate that the Bi!F-4,5-diol is more tumorigenic th at the parent hydrocarbon or the Bi!F-9,10-diol. A covalent DNA adduc t formed between the anti-Bi!F-4,5-diol epoxide and deoxyguanosine wa s the major species of DNA adduct formed in S. typhimurium. This adduc t corresponds to the major DNA adduct formed in mouse skin following a pplication Bi!F. (C) 1993 Wiley-Liss, Inc.