Journal Article

Metabolic Activation of Heterocyclic Amines and Expression of CYP1A1 in the Tongue

Mami Takiguchi, Wageh S. Darwish, Yoshinori Ikenaka, Marumi Ohno and Mayumi Ishizuka

in Toxicological Sciences

Volume 116, issue 1, pages 79-91
Published in print July 2010 | ISSN: 1096-6080
Published online March 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq087
Metabolic Activation of Heterocyclic Amines and Expression of CYP1A1 in the Tongue

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Xenobiotic metabolism in oral tissues, especially in the tongue, has never been reported. In the present study, the metabolic activation/detoxification ability of promutagens in the tongue and the expression levels of related enzymes were investigated. Quantitative PCR analysis of rat tongue demonstrated constitutive messenger RNA (mRNA) expression of numerous drug-metabolizing enzymes. In particular, we detected mRNA, protein expression, and enzymatic activity of cytochrome P450 (CYP)1A1 in the tongue tissue. Metabolic activation of promutagens in the tongue was estimated using benzo[a]pyrene or heterocyclic amines (HCAs), found in cooked meat and tobacco products. Metabolic activation levels of HCAs in the tongue were comparable to those in the liver. In contrast, the expression levels of glutathione-S-transferase (GST) and uridine diphosphate-glucuronosyltransferase (UGT) in the tongue were considerably lower compared with those in the liver, and as a result, the mutagenic activity in the tongue was not decreased by GST- or UGT-dependent conjugation. Treatment of rats with sudan III, a typical inducer of CYP1A1, resulted in markedly increased CYP1A1 mRNA, protein expressions, and CYP1A-dependent enzymatic and mutagenic activities. In addition, CYP1A1 mRNA expression in carcinoma cells (SAS) was induced by sudan III exposure. In conclusion, mutagenic activation of xenobiotics and an increased risk of cancer in the tongue were observed in this study. Furthermore, ingestion of drug-metabolizing enzyme inducers has the potential to increase the metabolic activation in the tongue tissue and increase the risk of biomolecular attack by promutagens.

Keywords: tongue; CYP1A1; heterocyclic amines; metabolic activation; mutagenicity

Journal Article.  6393 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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