Rat and hamster hepatocyte-mediated induction of SCEs and mutation in V79 cells and mutation of salmonella by aminofluorene and dimethylnitrosamine.
Aminofluorene (AF) and dimethylnitrosamine (DMN) were examined for their ability to induce multiple genetic endpoints after rat and hamster hepatocyte metabolic activation. The endpoints measured included mutations at the Na+/K+-ATPase (ouabain resistance) and hypoxanthine-guanine-phosphoribosyltransferase (6-thioguanine resistance) loci, and sister-chromatid exchanges (SCEs) in Chinese hamster V79 cells, and mutation of Salmonella typhimurium strains TA98 and TA100. AF, with rat and hamster hepatocyte activation, induced only low levels of mutations at either loci in V79 cells but did induce SCEs. Mutation of Salmonella by AF after hepatocyte activation also occurred and was a sensitive endpoint for detecting this aromatic amine. DMN induced high levels of mutations at both loci in V79 cells in addition to SCEs in the presence of hepatocytes from both species. DMN was also mutagenic to Salmonella, but only with hamster hepatocytes. Salmonella did not respond as strongly to DMN as the V70 cells. Hamster hepatocytes were more active than rat hepatocytes in activating both carcinogens. The results indicate the variable sensitivity of the genetic endpoints and species differences in activation for two potent chemical carcinogens.
D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004128:Dimethylnitrosamine / Q000633:toxicity*; D005449:Fluorenes / Q000633:toxicity*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D005449:Fluorenes; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; C012177:2-aminofluorene; D007041:Hypoxanthine Phosphoribosyltransferase; D000254:Sodium-Potassium-Exchanging ATPase; D004128:Dimethylnitrosamine