Evaluation of two suggested methods of deactivating organic carcinogens by molecular modification.
Earlier observations that substitution of the aromatic nucleus of an arylamino/nitro carcinogen with either a sulphonic acid substituent or two methyl groups placed ortho to the nitrogen substituent renders the molecule non-carcinogenic have been extended via studies conducted in vitro. 4-Aminobiphenyl-4'-sulphonic acid has been synthesized and found to be non-mutagenic in the Salmonella mutation assay when tested under conditions where 4-aminobiphenyl was mutagenic. It is concluded that this sulphonic acid derivative may prove non-carcinogenic to rodents. In contrast to the non-carcinogenicity and non-mutagenicity reported for 3,3',5,5'-tetramethylbenzidine, 3,5-dimethyl-4-aminobiphenyl is approximately as mutagenic as 4-aminobiphenyl. It is therefore concluded that this material is potentially carcinogenic and that the loss of mutagenic activity observed for tetramethylbenzidine may be a structurally specific rather than a general phenomenon. In contrast, 3,5-dimethyl-4-nitrobiphenyl was much less mutagenic than 4-nitrobiphenyl. 9,9'-Bijulolidyl, a derivative of 3,3',5,5'-tetramethylbenzidine, was also found to be non-mutagenic. The general significance of these findings to the employment of structure-activity relationships in the design of non-mutagenic/non-carcinogenic molecules is discussed.
D000611:Aminobiphenyl Compounds / Q000494:pharmacology*; D000818:Animals; D001560:Benzidines / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008958:Models, Molecular; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000494:pharmacology*
D000611:Aminobiphenyl Compounds; D001560:Benzidines; D002273:Carcinogens; D009153:Mutagens; D013451:Sulfonic Acids