Cytochrome P4501A induction, benzo[a]pyrene metabolism, and nucleotide adduct formation in fish hepatoma cells: Effect of preexposure to 3,3 ',4,4 ',5-pentachlorobiphenyl

In PLHC-1 hepatoma cells, benzo[a]pyrene (B[a]P) caused a maximum induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deeth ylation (EROD), after 4 to 8 h of exposure, depending on the B[a]P concentr ation. The decline of EROD activity at longer exposure times was probably c aused by the rapid metabolism of B[a]P in this system (57% metabolism withi n 4 h incubation). In subsequent experiments, PLHC-1 cells were preinduced with PCB 126 for 24 h and then received a dose of 10, 100, or 1,000 nM H-3- B[a]P. A 1-nM concentration of PCB 126 caused an 80-fold induction of CYP1A activity, resulting in an increase in B[a]P metabolism of less than 10%, e xcept at the highest concentration of B[a]P (1,000 nM), where a 50% increas e was observed. In another experiment, an 80-fold induction of CYP1A activi ty caused a 20% increase in the metabolism of B[a]P (100 nM), and RNA adduc t formation was increased approximately twofold. These results indicate tha t, at exposure concentrations up to 100 nM B[a]P, CYP1A activity is not rat e limiting for B[a]P metabolism. Furthermore, CYP1A seems to also be specif ically involved in B[a]P activation in PLHC-1 cells. However, CYP1A inducti on causes only a relatively small increase in activation, probably because of the action of other enzymes involved in B[a]P activation and deactivatio n.