The effect of liver postmitochondrial fraction concentration from Aroclor 1254-treated rats on promutagen activation in L5178Y cells.
L5178Y/TK+/- cells were treated with either N-acetyl-2-aminofluorene (AAF), 2-aminoanthracene (2A), benzanthracene (BA), benzo[a]pyrene (BP), 3-methylcholanthrene (3MCA), or dimethylnitrosamine (DMN) in the presence of varied concentrations (2.5-10% v/v) of liver S9 (9000 x g) postmitochondrial fraction from Aroclor 1254-dosed male CD rats. Consistent S9 concentration-dependent decreases in trifluorothymidine-resistant (TFTr) mutant induction were noted following 3 h exposure of L5178Y/TK+/- cells to either 2.5 micrograms/ml BP, 50 or 67 micrograms/ml AAF, 0.96 micrograms/ml 2A, 7.35 micrograms/ml BA, or 5.4 micrograms/ml 3MCA. The exception was DMN which yielded a moderate S9 concentration-dependent increase in TFTr mutant induction when L5178Y/TK+/- cells were treated for 3 h with 74.1 micrograms/ml DMN. Depending upon the promutagen being tested, these results suggest two different metabolic events: (1) activation via non-induced enzymes or other factors whose activities are totally S9 volume-dependent (DMN), and (2) deactivation via induced detoxification pathways, a sequence favored by increasing S9 concentration (all others). Utilization of a single "standard" (10%) concentration of liver S9 from Aroclor 1254-treated rats did not appear to provide optimal metabolic activation for 5 of these 6 promutagens.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D007940:Leukemia L5178 / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats
D001140:Aroclors; D002273:Carcinogens; D009153:Mutagens