Mutagenic activation of 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole(Trp-P-1) and 3-amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2) by primary cultures of adult rat hepatocytes: effect of Aroclor induction in vitro.
The mutagenic activation of tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, was studied in a Salmonella TA98/hepatocyte mutagenesis assay. Adult rat hepatocytes in primary culture were either untreated or induced by the addition of Aroclor 1254 (2 micrograms/ml) 18-20 h before the mutagenesis test which was performed at day 1 and at day 2 after the isolation of hepatocytes. The mutagenic activation of Trp-P-1 and Trp-P-2 was studied as a function of the time of incubation and of the concentration of chemical. Trp-P-1 and Trp-P-2 incubated for 20 min in the presence of untreated hepatocytes and bacteria gave rise to a weak number of revertants which doubled the level of spontaneous mutants. Aroclor-induced hepatocytes became highly competent in mutagenic activation of tryptophan pyrolysis products and the induction ratio reached 4.9 and 7.1 for Trp-P-1 and Trp-P-2, respectively, after 60 min of incubation, on day 2 of the experiment. It should be noted that the induction ratio was higher on day 2 than on day 1. When conditions were standardized, i.e. Aroclor-induced hepatocytes on day 2, final concentration of cellular protein about 1 mg/ml, 20 min of incubation, the Salmonella/hepatocyte assay produced a linear concentration-dependent mutagenic response for Trp-P-1 and Trp-P-2. By comparing the results obtained with Aroclor-induced hepatocytes and Aroclor-induced liver S9 fraction in the Salmonella test, it could be estimated that hepatocytes were 3 times less active than the S9 fraction with regard to mutagenic activation of both Trp-P-1 and Trp-P-2.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001711:Biotransformation; D002243:Carbolines / Q000633:toxicity*; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine); D007211:Indoles / Q000633:toxicity*; D007700:Kinetics; D008099:Liver / Q000166:cytology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D001140:Aroclors; D002243:Carbolines; D007211:Indoles; D009153:Mutagens; D020111:Chlorodiphenyl (54% Chlorine); C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D011078:Polychlorinated Biphenyls; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole