The possible role of azoreduction in the bacterial mutagenicity of 4-dimethylaminoazobenzene (DAB) and 2 of its analogues (6BT and 5I).
The extent to which azoreductive cleavage contributes to the bacterial mutagenicity of 3 azo compounds has been investigated. The compounds studied were the rodent-liver carcinogens 4-dimethylaminoazobenzene (DAB) and 6-dimethylaminophenylazobenzthiazole (6BT), and the reported non-carcinogenic isostere 5-dimethylaminophenylazoindoline (5I). Although each of these compounds is mutagenic to Salmonella when evaluated using a pre-incubation protocol and in the presence of an induced rat-liver S9 mix, the constituent amines (cleavage products) were essentially inactive. It is therefore concluded that the mutagenic response reported for DAB, 6BT and 5I is related to metabolic activation of the intact molecules. In addition, the non-mutagenicity of 4'-phenyl-4-dimethylaminoazobenzene (4PhDAB) suggests that azoreductase activity is low in the Salmonella preincubation assay, at least as conducted in this laboratory. In the case of 4PhDAB, less than 1.4% azoreduction would yield sufficient quantities of the derived amine, 4-aminobiphenyl, for a positive mutagenic response to have been observed.
D000818:Animals; D052160:Benzothiazoles; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000378:metabolism* / Q000494:pharmacology; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D052160:Benzothiazoles; D002273:Carcinogens; D009153:Mutagens; D013844:Thiazoles; C037353:5-dimethylaminophenylazoindazole; C012103:N,N-dimethyl-4-(6-benzothiazolylazo)aniline; D004124:p-Dimethylaminoazobenzene