人食管癌与NMBzA引起的人和猴食管上皮细胞中多种抑癌基因变化的相关性研究

CORRETLAION STUDIES ON THE ALTEEATIONS OF MULTIPLETUMOR SUPPRESSOR GENES IN HUMAN ESOPHAGEAL CANCER AND IN HUMAN AND MONKEY ESOPHAGEAL EPITHELIAL CELLS TREATED WITH N-METHYL-N-BENZYL NITROSAMINE

为了研究人原发性食管癌组织中多种抑癌基因突变谱与甲基苄基亚硝胺（ＮＭＢｚＡ）引起的人和猴食管上皮细胞中多种抑癌基因突变谱的相关性。我们应用ＰＣＲ扩增与直接测序技术分析了人原发性食管癌和ＮＭＢｚＡ处理的人和猴食管上皮细胞中多种抑癌基因ｐ５３，Ｒｂ，ＡＰＣ和ＭＣＣ的突变谱；发现４０．９％（９／２２）的人原发性食管癌ｐ５３基因突变与ＮＭＢｚＡ处理的人和猴食管上皮细胞中ｐ５３基因的突变相同，也发现ＮＭＢｚＡ引起的人和猴食管上皮细胞中多种抑癌基因Ｒｂ、ＡＰＣ、ＭＣＣ的突变谱与部分人原发性食管癌多种抑癌基因突变谱相同。首次从分子水平证明：ＮＭＢｚＡ引起的多种抑癌基因突变谱与人原发性食管癌的突变谱有相关性，从而验证了ＮＭＢｚＡ是我国食管癌的致病因子之一。

Abstract The correlation between mutation spectra of tumor suppressor genes Rb,p53,APC andMCC in human esophageal cancer(EC) and in human and monkey esophageal epithelium treated withN-Methyl-N-Benzyl nitrosamine(NMBzA ) was studied using PCR amplification and direct sequenc-ing methods. The results showed that in 40.9%(9/22 ) of the specimen examined , the mutationspectrum of p53 in primary EC was similar to that in the esophageal epithelium of human fetus(in vit-ro)and monkey(in vivo ) treated with NMBzA. The same mutational spectra of tumor suppressorgenes Rb , APC , MCC in esophageal epithelium cells of human and monkey treated with NMBzAwere also found in some human primary EC. The correlation observed in the mutation spectra of mul-tiple tumor suppressor genes between human primary EC and the esophageal epithelia of human andmonkey origin treated with NMBzA wouldsuggest that NMBzA may be the esophageal etiological a-gent for human esophageal cancer in China.