Using base-specific Salmonella tester strains to characterize the types ofmutation induced by benzidine and benzidine congeners after reductive metabolism

Although benzidine (Bz), 4-aminobiphenyl (ABP), 3,3'-dichlorobenzidine HCl (DCBz), 3,3'-dimethylbenzidine (DMBz), 3,3'-dimethoxybenzidine (DMOBz) and the benzidine congener-based dye trypan blue (TB) produce primarily framesh ift mutations in Salmonella typhimurium, the base-substitution strain TA100 also responds to these compounds when S9 is present. Performing DNA sequen ce analysis, other investigators have shown that ABP induces frameshift, ba se-pair and complex mutations. Also, it was found that an uninduced hamster liver S9 preparation with glucose-6-phosphate dehydrogenase, FMN, NADH and four times glucose 6-phosphate gave a stronger mutagenic response than the conventional plate incorporation with rat S9 activation mixture for all th e compounds tested. Using the base-specific tester strains of S. typhimuriu m (TA7001-TA7006) with the above reductive metabolic activation system, we surveyed these compounds for the ability to produce specific base-pair subs titutions after reductive metabolism. Bz was weakly mutagenic in TA7005 (0. 04 revertants/mug). ABP was mutagenic in TA7002 (1.4 revertants/mug), TA700 4 (0.6 revertants/mug), TA7005 (2.98 revertants/mug) and TA7006 (0.4 revert ants/mug). DCBz was weakly mutagenic in TA7004 (0.01 revertants/mug). It wa s concluded that benzidine induced some CG-> AT transversions in addition t o frameshift mutations. ABP induced TA-> AT, CG-> AT, and CG-> GC transvers ions as well as GC-> AT transitions. DCBz induced only GC-> AT transitions. Because DMBz, DMOBz and TB were not mutagenic in this base-substitution mu tagen detection system, their mutagenic activity was attributed strictly to frameshift mechanisms. (C) 2001 Published by Elsevier Science Ltd.