胃黏膜肠化生微粒体对环境致癌物的诱变激活作用。

Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with intestinal metaplasia.

作者信息

Tatemichi M, Nomura S, Ogura T, Sone H, Nagata H, Esumi H

机构信息

Investigative Treatment Division, National Cancer Center Research Institute East, Chiba, Japan.

出版信息

Cancer Res. 1999 Aug 15;59(16):3893-8.

PMID:10463577

Abstract

Coexpression of cytochrome P450 monooxygenases (CYPs) and reductase was found in human gastric mucosa with intestinal metaplasia. Immunohistochemistry showed reactivity to P450 reductase in metaplastic epithelial cells and in pyloric gland cells in glands showing intestinal metaplasia. These cells exhibit NADPH-diaphorase activity. Reverse transcription-PCR analysis and Western blotting showed that CYP1A1 and CYP1A2 were expressed in specimens with intestinal metaplasia. Tissue distribution of CYP1A1 coincided with that of P450 reductase. However, immunoreactivity to CYP1A2 protein was localized only in the pyloric gland cells near the intestinal metaplastic gland. Salmonella typhimurium mutagen assay definitively revealed that microsomes prepared from gastric mucosa with intestinal metaplasia, in particular in the pyloric gland, functionally activated benzo(a)pyrene and 2-amino-3-methylimidazo [4,5-f]quinoline. These results indicate that carcinogen activation by CYP enzymes expressed in the gastric mucosa may contribute to carcinogenesis of the stomach.

摘要

在具有肠化生的人胃黏膜中发现了细胞色素P450单加氧酶（CYPs）和还原酶的共表达。免疫组织化学显示，在显示肠化生的腺体中的化生上皮细胞和幽门腺细胞中，对P450还原酶有反应性。这些细胞表现出NADPH-黄递酶活性。逆转录-聚合酶链反应分析和蛋白质印迹显示，CYP1A1和CYP1A2在肠化生标本中表达。CYP1A1的组织分布与P450还原酶的分布一致。然而，对CYP1A2蛋白的免疫反应性仅定位在肠化生腺体附近的幽门腺细胞中。鼠伤寒沙门氏菌诱变试验明确显示，从具有肠化生的胃黏膜中制备的微粒体，特别是在幽门腺中，可功能性激活苯并(a)芘和2-氨基-3-甲基咪唑[4,5-f]喹啉。这些结果表明，胃黏膜中表达的CYP酶对致癌物的激活可能有助于胃癌的发生。