Studies on the metabolic activation of benzidine by isolated rat hepatocytes.
Isolated rat liver cells were shown to metabolize the aromatic amine benzidine to reactive products which are mutagenic to Salmonella typhimurium TA 1538 and which give rise to DNA excision repair within the liver cells. Intact rat liver cells are shown to be more active in the formation of mutagenic metabolites than the 9000-g supernatant from these cells. Data are presented which are in favour of the role of N-acetylation in this respect. Furthermore, indications are presented that a sulfation reaction is involved in the generation of DNA modifying metabolites, whereas formation of mutagenic products is likely to proceed via deacetylation and/or N,O-acyltransfer. Finally, data are given about the extrahepatocellular appearance of premutagenic metabolites which are more prone to metabolic activation by additional metabolic factors in the Salmonella assay than benzidine itself. The impact of these observations on the estimation of the genotoxic potential of benzidine will be discussed.
D000107:Acetylation; D000818:Animals; D001560:Benzidines / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D004260:DNA Repair / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains
D001560:Benzidines; D009153:Mutagens