Using base-specific Salmonella tester strains to characterize the types of mutation 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 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/microg). ABP was mutagenic in TA7002 (1.4 revertants/microg), TA7004 (0.6 revertants/microg), TA7005 (2.98 revertants/microg) and TA7006 (0.4 revertants/microg). DCBz was weakly mutagenic in TA7004 (0.01 revertants/microg). 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.
Claxton
L D
LD
Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA. claxton.larry@epa.gov
Hughes
T J
TJ
Chung
K T
KT
D015101:3,3'-Dichlorobenzidine / Q000378:metabolism / Q000633:toxicity; D000611:Aminobiphenyl Compounds / Q000378:metabolism / Q000633:toxicity; D001560:Benzidines / Q000633:toxicity*; D004269:DNA, Bacterial / Q000187:drug effects; D003962:Dianisidine / Q000378:metabolism / Q000633:toxicity; D016368:Frameshift Mutation; D005798:Genes, Bacterial / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*
D000611:Aminobiphenyl Compounds; D001560:Benzidines; D004269:DNA, Bacterial; D009153:Mutagens; C006757:4-biphenylamine; D015101:3,3'-Dichlorobenzidine; C029876:benzidine; D003962:Dianisidine