Mutagenesis induced by procarcinogens at the hypoxanthine-guanine phosphoribosyl transferase locus of human fibroblasts cocultured with rat hepatocytes.
The addition of diethylnitrosamine or cyclophosphamide in cultures of hepatocytes overlaid on confluent diploid human fibroblasts resulted in a dose-dependent increase in the frequency of hypoxanthine-guanine phosphoribosyl transferase human fibroblast mutants with both chemicals. Different toxicity patterns for the two cell types were seen. Diethylnitrosamine was more toxic to the hepatocytes, whereas cyclophosphamide was more toxic to the fibroblasts. These data open the possibility of using strains of human fibroblasts as in vitro screens for mutagenicity of procarcinogens.
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D009154:Mutation / Q000187:drug effects*; D009602:Nitrosamines / Q000494:pharmacology*; D051381:Rats
D009602:Nitrosamines; D004052:Diethylnitrosamine; D003520:Cyclophosphamide; D007041:Hypoxanthine Phosphoribosyltransferase