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United States Department of Agriculture

Agricultural Research Service


item Shappell, Nancy
item Carlino-macdonald, U
item Amin, S
item Kumar, S
item Sikka, H

Submitted to: Toxicological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2002
Publication Date: 1/1/2003
Citation: Shappell, N.W., Carlino-Macdonald, U., Amin, S., Kumar, S., Sikka, H.C. 2003. Comparative metabolism of chrysene and 5-methylchrysene by rainbow trout and rat liver microsomes. Toxicological Sciences. 72:260-266.

Interpretive Summary: Chrysene and 5-methylchrysene (5-MeC) are environmental pollutants that have different cancer-causing potential, the first weak, the second strong. These chemicals require metabolism by the animal to form metabolites which interact with DNA and cause cancer. We compared the metabolism of these chemicals using subcellular fractions (microsomes) from the liver of rats and shasta rainbow trout. Overall metabolite formation by liver microsomes was 13 times higher for rats than fish, but the rates were the same for both chrysene and 5-MeC By pretreating animals with 3-methylcholanthrene (3-MC), enzymes responsible for this metabolism can be induced, and rates of metabolism increased. With 3-MC treatment, the precursor to the metabolite that binds DNA represented 19% (rat) and 30% (trout)of total chrysene metabolites, while the DNA-binding precursor from 5-MeC represented only 12% (rat) and 6% (trout) of total metabolites. These results indicate that addition of the methyl group decreases the ability of the enzymes to form the DNA-binding metabolite. In addition, we found rat microsomes formed DNA-binding precursors at a rate twice that of trout microsomes.

Technical Abstract: We have investigated the metabolism of chrysene (CHR) and 5-methylchyrsene (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 vs. 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.

Last Modified: 10/17/2017
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