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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
Author(s) -
Smeets Jean M. W.,
Voormolen Adriaan,
Tillitt Donald E.,
Everaarts Jan M.,
Seinen Willem,
van den Berg Martin
Publication year - 1999
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.5620180316
Subject(s) - benzo(a)pyrene , pyrene , metabolism , chemistry , cytochrome p450 , cytochrome , adduct , nucleotide , toxicokinetics , enzyme , stereochemistry , biochemistry , organic chemistry , gene
In PLHC‐1 hepatoma cells, benzo[ a ]pyrene (B[ a ]P) caused a maximum induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O ‐deethylation (EROD), after 4 to 8 h of exposure, depending on the B[ a ]P concentration. The decline of EROD activity at longer exposure times was probably caused by the rapid metabolism of B[ a ]P in this system (57% metabolism within 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 3 H‐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%, except at the highest concentration of B[ a ]P (1,000 nM), where a 50% increase was observed. In another experiment, an 80‐fold induction of CYP1A activity caused a 20% increase in the metabolism of B[ a ]P (100 nM), and RNA adduct formation was increased approximately twofold. These results indicate that, at exposure concentrations up to 100 nM B[ a ]P, CYP1A activity is not rate limiting for B[ a ]P metabolism. Furthermore, CYP1A seems to also be specifically involved in B[ a ]P activation in PLHC‐1 cells. However, CYP1A induction causes only a relatively small increase in activation, probably because of the action of other enzymes involved in B[ a ]P activation and deactivation.