Definition of conditions for the detection of genotoxic chemicals in the adult rat-liver epithelial cell/hypoxanthine-guanine phosphoribosyl transferase (ARL/HGRPT) mutagenesis assay.
Conditions for the detection of genotoxic chemicals in the adult rat-liver epithelial cell/hypoxanthine-guanine phosphoribosyl transferase (ARL/HGPRT) mutagenesis assay have been defined. These included (1) a 3-day exposure to activation-dependent carcinogens; (2) a minimum of 14 days for induced mutant expression; (3) seeding density of 1 x 10(4) cells per cm2 for selection of mutants; (4) use of 6-thioguanine and (5) acceptance of genotoxicity of test chemicals if induced mutant incidence is significantly above that of the parallel run control and beyond the 98% confidence limits of the mean of the population spontaneous mutant incidence. With this protocol, the ARL/HGPRT mutagenesis assay has the capacity to activate representative members of the mycotoxin, aminoazo dye, aromatic amine and nitrosamine-types of carcinogens. This assay, offering additional metabolic parameters through intrinsic metabolic capability and providing a reliable end-point of clear biologic significance serves as a useful supplement to the Salmonella/microsome bacterial mutagenesis assay in a battery for the detection of genotoxic chemicals.
D000818:Animals; D002273:Carcinogens; D002453:Cell Cycle; D002478:Cells, Cultured; D004261:DNA Replication; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D009153:Mutagens; D051381:Rats; D013997:Time Factors
D002273:Carcinogens; D009153:Mutagens; D007041:Hypoxanthine Phosphoribosyltransferase