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

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Title: Metabolic Activation of Heterocyclic Amines and Expression of CYP1A1 in the Tongue
Authors: Takiguchi, Mami Browse this author
Darwish, Wageh S. Browse this author
Ikenaka, Yoshinori Browse this author →KAKEN DB
Ohno, Marumi Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: tongue
heterocyclic amines
metabolic activation
Issue Date: Jul-2010
Publisher: Oxford University Press
Journal Title: Toxicological Sciences
Volume: 116
Issue: 1
Start Page: 79
End Page: 91
Publisher DOI: 10.1093/toxsci/kfq087
PMID: 20308224
Abstract: 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 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 UDP-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, 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.
Rights: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Toxicological Sciences following peer review. The definitive publisher-authenticated version Toxicological Sciences 2010 116(1):79-91 is available online at:
Type: article (author version)
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石塚 真由美

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