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ToxSci Advance Access originally published online on March 7, 2003
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Toxicological Sciences 72, 260-266 (2003)
Copyright © 2003 by the Society of Toxicology

ENVIRONMENTAL TOXICOLOGY

Comparative Metabolism of Chrysene and 5-Methylchrysene by Rat and Rainbow Trout Liver Microsomes

Nancy W. Shappell*,1, Uli Carlino-MacDonald*,2, Shantu Amin{dagger}, Subodh Kumar* and Harish C. Sikka*,3

* Environmental Toxicology and Chemistry Laboratory, Great Lakes Center, State University of New York College at Buffalo, 1300 Elmwood Avenue, Buffalo, New York 14222; and {dagger} American Health Foundation, 1 Dana Road, Valhalla, New York

We have investigated the metabolism of chrysene (CHR) and 5-methychyrsene (5-MeCHR) by Shasta rainbow trout (Oncorhyncus mykiss) and Long Evans rat liver microsomes to assess the effect of a non-benzo ring methyl substituent on the reactions involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs). Trout as well as rat liver microsomes metabolized both CHR and 5-MeCHR at essentially similar rates, indicating that the methyl substituent does not alter the substrate specificity of the cytochrome P450(s) involved in the metabolism of the two PAHs. Dihydrodiols were the major CHR metabolites formed by both trout and rat liver microsomes, whereas the trout liver microsomes formed a considerably higher proportion of 5-MeCHR phenols compared to diols, indicating that 5-methyl substitution alters the substrate specificity of trout microsomal epoxide hydrolase for 5-MeCHR epoxides. Unlike trout liver microsomes, rat liver microsomes formed a much greater proportion of 5-MeCHR diols compared to 5-MeCHR phenols, suggesting that 5-MeCHR epoxides are better substrates for the microsomal epoxide hydrolase present in rat liver than for the enzyme in trout liver. Both trout and rat liver microsomes are more efficient at attacking the bay-region bond versus the non-bay-region double bond in chrysene. In contrast the reverse is true in the case of 5-MeCHR, indicating that a non-benzo ring methyl substituent alters the regioselectivity of the enzymes involved in the oxidative metabolism of PAHs.

Key Words: Shasta rainbow trout; Oncorhyncus mykiss; rat; liver microsomes; chrysene; 5-methylchrysene; metabolism; regioselectivity.


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