Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats
Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats
复制标题
大鼠胃肠道中杂环胺的代谢激活和异生物质代谢酶的表达
DOI：
10.1111/1750-3841.12931
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发表时间：
2015
期刊：
影响因子：
3.9
通讯作者：
Ishizuka M
中科院分区：
文献类型：
--
作者：
Darwish WS;Nakayama SMM;Itotani Y;Ohno M;Ikenaka Y;Ishizuka M
杂环胺主要通过摄入高温煎炸肉类进入人体。在输送到肝脏之前，胃肠道（GIT）暴露于摄入的异生物质可能会导致代谢激活，这可能解释了胃肠道致癌的高发生率。因此，本研究研究了 2 种杂环胺、2-氨基蒽 (2-AA) 和 3-氨基-1-甲基-5H-prydo[4,3-b]吲哚 (Trp-P-2) 在大鼠胃肠道中的诱变激活作用。此外，还检查了大鼠胃肠道中异生物质代谢酶（XME）的组成型 mRNA 表达谱。除十二指肠和直肠外，所有胃肠道组织中均检测到 2-AA 的代谢激活，并且在回肠和盲肠中检测到高水平。此外，我们发现空肠中 2-AA 和 Trp-P-2 的高代谢激活。大鼠GIT中I相和II相酶的mRNA表达与其诱变激活能力相对应。总之，我们的结果表明，GIT 组织中 XME 的不同表达水平可能导致大鼠杂环胺等异生物质代谢激活的组织特异性差异。
Heterocyclic amines get entry into human body mainly through ingestion of pan‐fried meats cooked at high temperatures. Exposure of the gastrointestinal tract (GIT) to ingested xenobiotics prior to delivery to the liver may lead to metabolic activation, which may explain the high incidence of GIT carcinogenesis. Therefore, this study investigated the mutagenic activation of 2 heterocyclic amines, 2‐aminoanthracene (2‐AA) and 3‐amino‐1‐methyl‐5H‐prydo[4,3‐b]indole (Trp‐P‐2), in the GIT of rats. In addition, the constitutive mRNA expression profiles of xenobiotic‐metabolizing enzymes (XMEs) in the GIT of rats were examined. Metabolic activation of 2‐AA was detected in all GIT tissues except the duodenum and rectum, and it was detected at high levels in the ileum and cecum. Furthermore, we revealed high metabolic activation of 2‐AA and Trp‐P‐2 in the jejunum. The mRNA expression of phase I and II enzymes in rat GIT corresponded with their mutagenic activation ability. In conclusion, our results suggest that different expression levels of XME among GIT tissues may contribute to the tissue‐specific differences in metabolic activation of xenobiotics such as heterocyclic amines in rats.