亚硝基诱发大鼠胃腺癌发生发展过程中p53,ras基因表达和突?…

目的 探讨Ｐ５３、ｒａｓ基因在亚硝基胍诱发大鼠胃腺癌发生发展过程中的作用。方法 用免疫组织化学、聚合酶链反应－单链构象多态怀分析（ＰＣＲ－ＳＳＣＰ）技术对大鼠正常腺胃粘膜、癌前病变和胃腺癌组织中ｐ５３、ｒａｓ基因的表达和突变进行检测。结果Ｐ５３蛋白在癌组织 的了性表达率为５０％,正常和癌前病缲为阴性;ｒａｓ蛋白癌前病变组织中阳性率为４４％,在癌组织中为２３％。癌组织中ｐ５３基因突变率为４５％,非

Expression and mutation of p53 and H-ras genes in the carcinogenesis and development of gastric adenocarcinoma induced by MNNG in rats

OBJECTIVE: To investigate the effect of p53 and H-ras genes in the carcinogenesis of and development of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats. METHODS: The expression of p53 and H-ras genes in normal mucosa, precancerous lesions and induced-cancers were studied immunohistochemically. DNA isolated from the precancerous lesion and tumors were analysed by PCR-SSCP for exon 5-8 of p53 gene and exon 1 and 2 of H-ras gene. RESULTS: p53 protein were detected in 50% (20/40) of the gastric cancers studied, but not in the precancerous lesion, while p21 ras protein seen in 23% (9/40) of the gastric cancers and 44% (23/52) of the precancerous lesions. p53 gene mutations were detected in 45% (18/40) of the cancers and none in the precancerous lesions by PCR-SSCP. H-ras gene mutation was not found in either the cancers or the precancerous lesions. CONCLUSIONS: The activation of ras gene is an early event and may be involved in the carcinogenesis of gastric cancer induced by MNNG. Inactivation of p53 gene may influence the development of the cancer.