【摘要】 目的 :研究 p5 3基因在肝癌发生过程中的作用。方法 :纯系 F344大鼠经 0 .0 6% 3′-甲基 -4-二甲胺基偶氮苯饲喂 6、1 2和 2 4周致癌。激光显微切取肝脏癌前病变和癌灶 ( LCM样品 ) ,进行p5 3基因的 PCR- SSCP分析和直接测序。结果 :2 5 %癌前病变 LCM样品及 45 .8%癌 LCM样品分别在外显子 6/7或 (和 ) 8呈现 PCR- SSCP电泳带移动率改变 ( P>0 .0 5 )。 2 0 .5 %癌前病变 LCM样品在外显子 6/7或 (和 ) 8发生了错义突变 ,显著低于癌灶样品 ( 62 .5 % ,P<0 .0 1 )。在较晚的癌前病变和癌灶细胞核中发现变异的 p5 3蛋白。结论 :p5 3基因突变始发于肝脏化学性癌发生早期的癌前病变 ,提示突变导致 p5 3基因的失活是肝癌发生的重要原因更多还原

【Abstract】 Objective:In order to study on effect of p53 gene on the hepatocarcinogenesis. Methods:The F344 rats were feed with 0.06% 3′ Methyl 4 dimethylaminoazobenzene for 6,12 and 24 W, respectively. The prehepatocarcinoma foci and hepatocarcinoma foci in their livers were sampled with Laser capture microdissection (LCM) and PCR SSCP analysis and direct sequencing of p53 gene were done after extracting DNA. Results: Alterations of PCR SSCP bands at exon 6/7 and 8 of p53 gene were found in 25%, LCM samples from prehepatocarcinoma and 45.8% of LCM specimens from hepatocarcinoma, but there was no significant difference between both groups, ( P >0.05). 20.5% of prehepatocarcinoma LCM samples presented missense mutation at exon 6/7 or/and 8, and was markedly lower than that of hepatocarcinoma specimens (62.5%) ( P <0.01). The mutant p53 protein was found in the cell nuclear of prehepatocarcinoma foci at later stage of experiment and hepatocarcinoma foci. Conclusion: p53 gene mutation was initiated at the early stage of prehepatocarcinoma foci in hepatocarcinogenesis, suggesting that the inactivation of p53 gene induced by mutation is an important factor of hepatocarcinogenesis. [更多还原