|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1998 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1997 : ¥2,000,000 (Direct Cost : ¥2,000,000)
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.