Activation of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-aminofluorene for bacterial mutagenesis by primary monolayer cultures of adult rat hepatocytes.
Primary monolayer cultures of adult rat hepatocytes readily activate 2-amino-3-methylimidazo[ 4,5-f ]quinoline (IQ), a potent bacterial mutagen (Ames test) present in some cooked foods. In a co-culture system consisting of intact hepatocytes, bacteria, and IQ, the number of revertant colonies produced increased proportionately with hepatocyte density to a maximum at about 6 X 10(5) hepatocytes. When the density exceeded 6 X 10(5) hepatocytes per dish, the number of revertant colonies markedly declined. The decline was not due to bacterial death. In standard Ames tests disrupted hepatocytes prepared from similarly handled monolayer cultures or from hepatocytes just after isolation (uncultured), or rat-liver S9, were only about 1/10th as efficient as the co-cultured intact hepatocytes (at optimum density) in activating IQ for bacterial mutagenesis. In contrast, 2-aminofluorene was poorly activated by intact hepatocytes. Disrupted hepatocytes and rat-liver S9 in standard Ames tests were much more effective than co-cultured intact hepatocytes in activating 2-aminofluorene for bacterial mutagenesis. For intact hepatocytes an inhibitor of cytochrome P-450, 2-[(2,4-dichloro-6-phenyl)-phenoxyl]ethylamine, inhibited IQ activation by 94-98%, and AF activation by 64-70%.
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D005449:Fluorenes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium
D005449:Fluorenes; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C012177:2-aminofluorene