NMBzA对人胎儿食管上皮组织中多种抑癌基因作用的研究

MULTIPLE TUMOR SUPPRESSOR GENES IN ESOPHAGEAL CARCINOMA INDUCED IN HUMAN FETUS ESOPHAGEAL EPITHELIUM BY NMBzA

流行病学研究表明，食管癌与环境中亚硝胺致癌物有密切关系。为了从分子水平阐明亚硝胺致癌物诱发食管癌癌变机制，作者应用ＰＣＲ扩增分析发现甲基苄基亚硝胺（ＮＭＢｚＡ）诱发的人胎儿食管癌组织有抑癌基因Ｒｂ、ｐ５３、ＡＰＣ和ＭＣＣ缺失。ＮＭＢｚＡ处理２４小时和３周的人胎儿食管上皮细胞中未发现这些基因的缺失；但ＰＣＲ直接测序分析发现ＮＭＢｚＡ体外处理３周的人胎儿食管上皮组织有ｐ５３、Ｒｂ和ＭＣＣ基因突变。以上体外实验首次证明：亚硝胺致癌物能引起人食管上皮细胞多种抑癌基因改变。亚硝胺致癌物引起的食管癌癌变中抑癌基因在早期阶段发生突变，在晚期阶段发生丢失，这对于从分子水平论证食管癌的亚硝胺病因具有重要意义。

Abstract Results of epidemiological studies have shown that nitrosamine-induced carcinogensis is in-volved in esophageal cancer in China. In order to demonstrate the mechanism at molecular level,Multiple tumor suppressor genes Rb, p53, APC and MCC in human fetusesophageal epitheliumtreated with NMBzA(in vitro) for 24 hours or three weeks and esophageal carcinoma induced byNMBzA were analyzed with PCR amplification and direct sequencing. In PCR amplification anal-ysis. Rb, p53, APC and MCC deletions in esophageal carcinoma of human fetus induced by NM-BzA were found, but no deletions of these genes was demonstrated in NMBzA-treated human fe-tal esophageal epithelium. PCR direct sequencing analysis revealed mutation of p53, Rb and MCCgenes in human fetal esophageal epithelium treated with NMBzA for three weeks. The resultsfirst confimed(in vitro)that nitrosamine can cause mutations and deletions of multiple tumorsuppressor genes in human esophageal epithelium.The mutations of tumor suppressor genes innitrosamine-induced esophageal carcinoma may occur in the early stage, while deletions in latestage of carcinogenesis.