Comparative metabolism of chrysene and 5-methylchrysene by rat and rainbow trout liver microsomes

Nancy W. Shappell, Uli Carlino-MacDonald, Shantu Amin, Subodh Kumar, Harish C. Sikka

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)260-266
Number of pages7
JournalToxicological Sciences
Volume72
Issue number2
DOIs
StatePublished - Apr 1 2003

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Trout
Oncorhynchus mykiss
Liver Microsomes
Metabolism
Liver
Rats
Polycyclic Aromatic Hydrocarbons
Epoxide Hydrolases
Phenols
Epoxy Compounds
Substrate Specificity
Long Evans Rats
Substrates
Enzymes
5-methylchrysene
chrysene
Regioselectivity
Cytochrome P-450 Enzyme System
Metabolites
Substitution reactions

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Shappell, Nancy W. ; Carlino-MacDonald, Uli ; Amin, Shantu ; Kumar, Subodh ; Sikka, Harish C. / Comparative metabolism of chrysene and 5-methylchrysene by rat and rainbow trout liver microsomes. In: Toxicological Sciences. 2003 ; Vol. 72, No. 2. pp. 260-266.
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Comparative metabolism of chrysene and 5-methylchrysene by rat and rainbow trout liver microsomes. / Shappell, Nancy W.; Carlino-MacDonald, Uli; Amin, Shantu; Kumar, Subodh; Sikka, Harish C.

In: Toxicological Sciences, Vol. 72, No. 2, 01.04.2003, p. 260-266.

Research output: Contribution to journalArticle

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