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-硝基喹啉1-氧化物（4 NQO）诱导的大鼠肿瘤模型中，p53蛋白过度表达。为探讨该实验模型中p53基因突变的发生率及其发生时间，我们对p53基因第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4 NQO溶液作为饮用水，持续4、8、12、16、20或24周，另设5只动物作为对照。在p53基因第8外显子限制性检测到SSCP迁移率改变。我们在30只大鼠中的6只中观察到p53突变; 12周组2只，16周组2只，20周组1只，24周组2只。由于大多数癌在4 NQO刺激20周后出现，这些结果阐明了在该癌模型中一些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.