Metabolic activation of heterocyclic amines and expression of CYP1A1 in the tongue
Metabolic activation of heterocyclic amines and expression of CYP1A1 in the tongue
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舌头中杂环胺的代谢激活和 CYP1A1 的表达
DOI：
10.1093/toxsci/kfq087
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发表时间：
2010
期刊：
影响因子：
3.8
通讯作者：
Ishizuka M.
中科院分区：
文献类型：
--
作者：
Takiguchi M;Darwish WS;Ikenaka Y;Ohno M;Ishizuka M.
在口腔组织中，特别是在舌头中，外源性生物代谢从未被报道过。本研究探讨了舌中前致突变物的代谢活化/解毒能力及相关酶的表达水平。定量PCR分析表明，大鼠舌组成的信使RNA（mRNA）表达的许多药物代谢酶。特别地，我们检测了舌组织中细胞色素P450（P450）1A 1的mRNA、蛋白表达和酶活性。使用熟肉制品和烟草制品中发现的苯并[a]芘或杂环胺（HCAs）估计舌头中前诱变剂的代谢活化。舌头中HCAs的代谢活化水平与肝脏中的代谢活化水平相当。与此相反，谷胱甘肽-S-转移酶（GST）和尿苷二磷酸-葡萄糖醛酸转移酶（UGT）的表达水平在舌头中的肝脏相比，是相当低的，因此，在舌头的诱变活性并没有减少GST或UGT依赖的共轭。苏丹III，一个典型的诱导剂的CYP 1A 1的大鼠治疗，导致显着增加CYP 1A 1 mRNA，蛋白质表达，CYP 1A依赖的酶和致突变活性。另外，苏丹Ⅲ还可诱导癌细胞（SAS）中CYP 1A 1 mRNA的表达。总之，在本研究中观察到外源性物质的致突变激活和舌癌风险增加。此外，摄入药物代谢酶诱导剂有可能增加舌组织的代谢活化，并增加前诱变剂生物分子攻击的风险。
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.