SSCP Analysis of p53 in the Development of Rat Tongue Carcinoma Induced by 4-Nitroquinoline 1-oxide

SSCP 分析 p53 在 4-硝基喹啉 1-氧化物诱导的大鼠舌癌发展中的作用

• 批准号: 09672084
• 负责人: UENO Shigeru
• 金额: $ 1.47万
• 依托单位: Osaka Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672084/
• 关键词: p53 gene; carcinogenesis; rat; oral carcinoma; 4-nitroquinoline 1-oxide(4NOO); SSCP; oval carcinoma; 4NQO; Corcinogenesis; oral carcinoma; 4NQ0; mutation

Mutations in the p53 gene have been implicated in the pathogenesis of a wide variety of human neoplasms. Our previous study revealed an overexpression of p53 protein in a 4-nitrocjuinoline 1-oxide (4NQO)-induced rat carcinoma model. To investigate the incidence of p53 mutation and the time of its occurrence in this experimental model, we performed a single-strand conformation polymorphism (SSCP) analysis on exons 5, 6, 7 and 8 of p53 gene. In the present study, 30 rats were divided into 6 equal groups and given 50 ppm 4NQO solution as drinking water for 4, 8, 12, 16, 20 or 24 weeks ; another 5 animals were used as controls. SSCP mobility shifts were restrictively detected in exon 8 of p53. We observed p53 mutations in 6 of 30 rats ; 2 in the 12-week group, 2 in the 16-week group, one in the 20-week group and 2 in the 24-week group. Since most of the carcinomas appeared after 20 weeks of 4NQO stimuli, these results clarified that some of the p53 mutations occurred in the premalignant stage in this carcinoma model.

p53基因的突变与多种人类肿瘤的发病机制有关。我们之前的研究发现，在4-硝基喹啉1-氧化物（4NQO）诱导的大鼠癌模型中p53蛋白过表达。为了研究该实验模型中p53突变的发生率及其发生时间，我们对p53基因的5、6、7和8外显子进行了单链构象多态性（SSCP）分析。本研究将30只大鼠分为6组，分别给予50 ppm的4NQO溶液作为饮用水，连续饮水4、8、12、16、20和24周；另外5只动物作为对照。在p53的第8外显子中限制性地检测到SSCP迁移位移。我们在30只大鼠中观察到6只p53突变；12周组2例，16周组2例，20周组1例，24周组2例。由于大多数癌是在4NQO刺激20周后出现的，因此这些结果表明，在该癌模型中，一些p53突变发生在癌前阶段。