Fujimoto Y, Hampton L L, Snyderwine E G, Nagao M, Sugimura T, Adamson R H, Thorgeirsson S S
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Jpn J Cancer Res. 1994 May;85(5):506-9. doi: 10.1111/j.1349-7006.1994.tb02387.x.
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of several heterocyclic amines formed during the cooking of proteinaceous foods. IQ is a potent carcinogen in rodent bioassays and causes a high incidence of hepatocellular carcinomas in nonhuman primates. We examined 20 hepatocellular carcinomas (HCCs) from nonhuman primates for mutations of the p53 gene using polymerase chain reaction-single strand conformational polymorphism analysis. Mutations in the p53 gene were detected in 4 of 20 HCCs (20%) with 3 showing G-to-T transversions and one a G-to-A transition. Three of these mutations were observed in codons 175 and 248 that are known mutational hot spots in human cancers. These data indicate that part of the IQ-induced HCCs in nonhuman primates may involve inactivation of the p53 gene and suggest that IQ and possibly other heterocyclic amines may participate in human carcinogenesis by a similar mechanism.
2-氨基-3-甲基咪唑并[4,5-f]喹啉（IQ）是在蛋白质类食物烹饪过程中形成的几种杂环胺之一。IQ在啮齿动物生物测定中是一种强效致癌物，并且在非人类灵长类动物中会导致肝细胞癌的高发病率。我们使用聚合酶链反应-单链构象多态性分析，检测了来自非人类灵长类动物的20例肝细胞癌（HCC）中p53基因的突变情况。在20例HCC中有4例（20%）检测到p53基因的突变，其中3例显示G到T的颠换，1例为G到A的转换。这些突变中有3例出现在密码子175和248，这两个密码子是人类癌症中已知的突变热点。这些数据表明，非人类灵长类动物中部分由IQ诱导的HCC可能涉及p53基因的失活，并提示IQ以及可能其他杂环胺可能通过类似机制参与人类致癌过程。
