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

P53基因突变与多种人类肿瘤的发病机制有关。我们先前的研究发现，在4-硝基-1-氧化物(4NQO)诱导的大鼠肿瘤模型中，P53蛋白过表达。为了探讨P53基因突变的发生率和发生的时间，我们对P53基因的第5、6、7和8外显子进行了单链构象多态性分析。本研究将30只大鼠分为6组，分别给予50ppm的4NQO溶液饮用4、8、12、16、20、24周，另5只动物作为对照组。限制性地检测到P53外显子8的SSCP迁移率的变化。我们观察了30只大鼠中的6只，其中2只在12周组，2只在16周组，1只在20周组，2只在24周组。由于大多数癌是在4NQO刺激20周后出现的，这些结果表明，在该癌模型中，一些P53突变发生在癌前阶段。

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.