Metabolic activation of N-acetylbenzidine and N,N'-diacetylbenzidine to mutagens, using isolated hepatocytes and the 9000 X g liver supernatant from rat, hamster and guinea pig.
The metabolic activation of MABZ and DABZ, forming products mutagenic towards Salmonella typhimurium TA1538, was studied with isolated hepatocytes from rat, hamster and guinea pig and the S9 fraction (9000 X g supernatant) prepared from these hepatocytes. Special attention was given to the influence of acetyl-CoA, the cofactor for N-acetylation, on the mutagenicity of these arylamides. The rat and guinea pig S9 preparation activated MABZ as well as DABZ to a much higher degree than the intact hepatocytes of these animal species. Addition of acetyl-CoA to the S9 preparation decreased the mutagenicity of MABZ and DABZ. On the contrary, for the hamster the mutagenicity of MABZ and DABZ appeared to be lower with the S9 preparation than with intact hepatocytes. Addition of acetyl-CoA to the S9 here increased the mutagenic activity of these arylamides. In the presence of intact hepatocytes obvious interspecies differences were observed in the activation of MABZ and DABZ. DABZ was far more effectively activated by hamster hepatocytes than by rat hepatocytes. This was not found with MABZ. Both substrates were poorly activated by guinea pig hepatocytes.
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D001560:Benzidines / Q000378:metabolism*; D001711:Biotransformation; D006224:Cricetinae; D006168:Guinea Pigs; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D001560:Benzidines; D009153:Mutagens; C007291:N,N'-diacetylbenzidine; D000105:Acetyl Coenzyme A; C034938:N-acetylbenzidine