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Metabolism of phenanthrene by house fly CYP6D1 and dog liver cytochrome P450
Author(s) -
Korytko Peter J.,
Quimby Fred W.,
Scott Jeffrey G.
Publication year - 2000
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/(sici)1099-0461(2000)14:1<20::aid-jbt3>3.0.co;2-d
Subject(s) - phenanthrene , chemistry , metabolism , cytochrome p450 , microsome , environmental chemistry , drug metabolism , cytochrome , biochemistry , in vitro , enzyme
Polycyclic aromatic hydrocarbons (PAHs) are a ubiquitous class of environmental contaminants. The compound phenanthrene is a model PAH. A novel fluorometric method for measuring phenanthrene metabolism in vitro was developed and verified with direct measurement of [ 14< C]phenanthrene using dog liver microsomes. The fluorometric assay and direct measurement of [ 14 C]phenanthrene metabolism were used to show that CYP6D1, a house fly cytochrome P450, is the major house fly P450 involved in phenanthrene metabolism. Phenanthrene was metabolized by microsomes from the LPR strain of house fly that overexpresses CYP6D1, but metabolism was not observed in the CS strain that has a lower level of CYP6D1. Furthermore, the majority of phenanthrene metabolism was inhibited by a CYP6D1‐specific antibody. This study increases the number of known substrates of CYP6D1 and identifies polyaromatic hydrocarbons as potential substrates of CYP6D1. The utility of CYP6D1 as an agent in bioremediation and the utility of the new fluorometric assay for understanding PAH metabolism in insects and mammals are discussed. © 1999 John Wiley & Sons, Inc. J Biochem Toxicol 14: 20–25, 2000