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
Environmental Toxicology and Chemistry
By: J.M.W. Smeets, A. Voormolen, D. E. Tillitt, J.M. Everaarts, W. Seinen, and Vanden Berg
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Abstract
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 3H-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 he 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.
Suggested Citation
Smeets, J., Voormolen, A., Tillitt, D.E., Everaarts, J., Seinen, W., and Berg, V., 1999, 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: Environmental Toxicology and Chemistry, v. 18, no. 3, p. 474-480, https://doi.org/10.1002/etc.5620180316.
| Publication type | Article |
|---|---|
| Publication Subtype | Journal Article |
| Title | 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 |
| Series title | Environmental Toxicology and Chemistry |
| DOI | 10.1002/etc.5620180316 |
| Volume | 18 |
| Issue | 3 |
| Publication Date | March 01, 1999 |
| Year Published | 1999 |
| Language | English |
| Publisher | Wiley |
| Contributing office(s) | Columbia Environmental Research Center |
| Description | 7 p. |
| First page | 474 |
| Last page | 480 |