Enhancement by butylated hydroxytoluene of the in vitro activation of 3,3'-dichlorobenzidine.
Mutagenicity of Salmonella TA98 and covalent binding to DNA of 3,3'-dichlorobenzidine (DCB) were used to assess the influence of di-tert.-butylated hydroxytoluene (BHT) on the in vitro activation of the arylamine by rat hepatic S9 metabolic systems. BHT at a concentration of 4 or 20 microM enhanced the mutagenicity of DCB by 32 or 21%, respectively, and the covalent binding of DCB to added DNA by 76 or 328%, respectively. The antioxidant altered the HPLC profile of isolable DCB metabolites, causing a decrease in the formation of three metabolites, an increase in the formation of one metabolite, and the formation of an entirely new metabolite. BHT inhibited the mutagenicity of the promutagen 2-acetylaminofluorene (2-AAF) but had no effect on that of the direct-acting mutagen 2,4- dinitrophenylhydrazine (DNPH). The results show that BHT enhances the mutagenicity of and DNA binding by DCB, in contrast with the predominantly inhibitory effect of the antioxidant on the mutagenicity of other chemicals that require bioactivation.
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Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08855-0789.
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D015101:3,3'-Dichlorobenzidine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009152:Mutagenicity Tests; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D002084:Butylated Hydroxytoluene; D015101:3,3'-Dichlorobenzidine; D004247:DNA