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Identification of cytochrome P4501A inducers in complex mixtures of PAHs

Conference ·
OSTI ID:242318
; ;  [1]
  1. Univ. of Wisconsin, Stevens Point, WI (United States)
An in vitro ethoxyresorufin-O-deethylase (EROD) assay was used to determine the ability of various PAHs and PAH mixtures to induce Ah receptor mediated cytochrome P4501A activity in PLHC-1 fish hepatoma cells. The purpose of this study was to identify the most potent inducers of a complement of thirteen separate PAHs and describe the interactions occurring in complex mixtures of the same. Analysis of individual PAHs at both equal concentrations and concentrations at which they were present in a model environmental sample showed chrysene, benzo(k)fluoranthene (BKF), benzo(b)fluoranthene, and benzo(a)anthracene to be the most potent cytochrome P4501A inducers of the thirteen PAHs tested. At equal concentrations, they yielded maximum EROD activities of 740, 380, 130, and 55 pmol/min/mg respectively. Although maximum activity was lower, 135, 75, 25, and 10 pmol/min/mg respectively, they remained the most potent inducers at model environmental concentrations, even at concentrations as little as 5% those of more abundant PAHs. Analysis of various mixtures of the thirteen PAHs provided evidence of complex interactions. The mixtures tested did not conform to an additive model generated from individual PAH analyses. Many PAHs, even those which caused little or no cytochrome P4501A induction individually, acted in an antagonistic manner in mixtures with more potent inducers. All mixtures lacking chrysene and/or BKF showed markedly lower induction than mixtures containing those compounds. Overall, this approach was a rapid and useful method for identifying Ah active PAHs and describing their interactions in complex mixtures. Such information could proved useful in efforts to understand biological effects of complex mixtures of PAHs in environmental samples.
OSTI ID:
242318
Report Number(s):
CONF-9511137--; ISBN 1-880611-03-1
Country of Publication:
United States
Language:
English