Mutagenicity of 7H-dibenzo[c,g]carbazole and metabolites in Salmonella typhimurium.
7H-Dibenzo[c,g]carbazole (DBC) is a potent carcinogen of environmental import. Reverse-mutation plate-incorporation assays for mutagenicity were undertaken in Salmonella typhimurium strains TA98 and TA100. Results were negative when no exogenous activation system was used, as well as when assays incorporated liver homogenates (S9) from rats, mice and rabbits. By contrast DBC was mutagenic in a forward mutation assay in Salmonella strain TM677 using resistance to 8-azaguanine for selection. Metabolites of DBC were generated by incubation with rat-liver microsomes and separated by HPLC. Two of these metabolites were directly mutagenic for Salmonella strain TM 677 while two others were mutagenic upon addition of S9. Synthetic phenolic derivatives of DBC were also mutagenic in this assay when further metabolized. It is likely that metabolites of DBC phenols constitute the biologically active forms.
Schoeny
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R
Warshawsky
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D
D000818:Animals; D001711:Biotransformation; D002227:Carbazoles / Q000378:metabolism / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009154:Mutation; D011817:Rabbits; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D002227:Carbazoles; D002273:Carcinogens; D009153:Mutagens; C013478:7H-dibenzo(c,g)carbazole