The direct mutagenicity of aflatoxin B1 and metabolites to Salmonella typhimurium: structure mutagenicity relationships and mechanisms of action.
The non-microsomal mutagenesis of a series of aflatoxins in Salmonella typhimurium TA100 and TA98 was evaluated. Aflatoxin B1 had the highest direct or non-microsomal potency. However, the order of direct mutagenic activity as compared to indirect or microsomal activity was as follows; aflatoxin Q1 much greater than G1 greater than B1 greater than aflatoxicol. This order was determined using a new plotting strategy for identification of direct contribution to the mutagenesis, an I-D graph (indirect vs. direct activities). It is suggested from our analyses that the fused carbonyl bearing rings in aflatoxins are necessary for direct mutagenesis. This activity is facilitated by oxygen substitution at the terminal carbonyl ring. On the other hand, the cyclopentene structure may either attenuate or amplify the microsome mediated mutagenesis which is assumed to be produced by the vinyl ether portion of the molecule. This was dependent upon substitution at the cyclopentene. Stereo-sensitivity was revealed by the greater mutagenicity of unnatural aflatoxicol over the natural epimer. These observations point to a need for further study of direct binding and transmolecular-structure-activity relationships in order to fully develop the mechanism of aflatoxin mutagenicity.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics*; D013329:Structure-Activity Relationship
D000348:Aflatoxins; D007202:Indicators and Reagents; D009153:Mutagens; D016604:Aflatoxin B1