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

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

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

Takiguchi, Mami; Darwish, Wageh S.; Ikenaka, Yoshinori et al.

Toxicological Sciences, 2010, 116(1), 79-91

Permalink : https://hdl.handle.net/2115/44974

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アクセス権	open access
URI	https://hdl.handle.net/2115/44974
タイトル	Metabolic Activation of Heterocyclic Amines and Expression of CYP1A1 in the Tongue
著者	Takiguchi, Mami ; Darwish, Wageh S. ; Ikenaka, Yoshinori ; Ohno, Marumi ; Ishizuka, Mayumi
著者名 Takiguchi, Mami
著者名 Darwish, Wageh S.
e-Rad_Researcher 40543509 著者名 Ikenaka, Yoshinori
著者名 Ohno, Marumi
e-Rad_Researcher 50332474 著者名 Ishizuka, Mayumi
言語	英語
キーワード	tongue
	CYP1A1
	heterocyclic amines
	metabolic activation
	mutagenicity
発行日	2010-07
出版者	Oxford University Press
収録物名	Toxicological Sciences
巻(号)	116(1)
ページ	79-91
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	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: http://toxsci.oxfordjournals.org/cgi/content/abstract/116/1/79
PISSN	1096-6080
関連情報	PMID 20308224
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1093/toxsci/kfq087