Using base-specific Salmonella tester strains to characterize the types of mutation induced by benzidine and benzidine congeners after reductive metabolism (original) (raw)

2001, Food and Chemical Toxicology

Although benzidine (Bz), 4-aminobiphenyl (ABP), 3,3 0 -dichlorobenzidine HCl (DCBz), 3,3 0 -dimethylbenzidine (DMBz), 3,3 0dimethoxybenzidine (DMOBz) and the benzidine congener-based dye trypan blue (TB) produce primarily frameshift mutations in Salmonella typhimurium, the base-substitution strain TA100 also responds to these compounds when S9 is present. Performing DNA sequence analysis, other investigators have shown that ABP induces frameshift, base-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 the compounds tested. Using the base-specific tester strains of S. typhimurium (TA7001-TA7006) with the above reductive metabolic activation system, we surveyed these compounds for the ability to produce specific base-pair substitutions after reductive metabolism. Bz was weakly mutagenic in TA7005 (0.04 revertants/mg). ABP was mutagenic in TA7002 (1.4 revertants/mg), TA7004 (0.6 revertants/mg), TA7005 (2.98 revertants/mg) and TA7006 (0.4 revertants/mg). DCBz was weakly mutagenic in TA7004 (0.01 revertants/mg). It was concluded that benzidine induced some CG->AT transversions in addition to frameshift mutations. ABP induced TA->AT, CG->AT, and CG->GC transversions as well as GC->AT transitions. DCBz induced only GC->AT transitions. Because DMBz, DMOBz and TB were not mutagenic in this base-substitution mutagen detection system, their mutagenic activity was attributed strictly to frameshift mechanisms. # (92-87-5); 4-aminobiphenyl (92-67-1); 3,3 0 -dichlorobenzidine (91-94-1); 3,3 0 -dimethylbenzidine (119-93-7); 3,3 0 -dimethoxybenzidine (119-90-4); Trypan blue (72-57-1) 0278-6915/01/$ -see front matter # 2001 Published by Elsevier Science Ltd. P I I : S 0 2 7 8 -6 9 1 5 ( 0 1 ) 0 0 0 7 2 -2