p53基因在人食管诱发癌中的突变

p53 gene mutations in human esophageal cancer and human esophageal tissues treated with AMN

目的 :了解抑癌基因p5 3在人食管癌及其癌旁组织中的突变和致癌作用。方法 :采用PCR SSCP和DNA序列分析等方法对 2 4例人食管鳞状细胞癌术后标本和 2 1例移植到重度完全性免疫缺陷 (severecombinedimmunodefi cient,SCID)小鼠并用或不用N -戊基 -N -甲基亚硝基胺 (N amyl N methylnitrosamine ,AMN)处理的人食管正常组织标本 ,进行了p5 3基因外显子 4～ 8的突变研究分析。结果 :在食管癌组织及癌旁组织均检测出p5 3基因突变 ,其中食管癌组织标本中有 18个突变 ,癌旁组织标本中有 10个 ( 10 /17,5 8 8% )突变 ,主要的突变为G A转换。在 14例用AMN处理的人食管正常组织标本中出现 6个 ( 4 2 9% )突变 ;其中密码子 2 83的突变为G A转换。在人食管癌及其癌旁组织中p5 3基因的突变概率差异无统计学意义。结论

OBJECTIVE:To characterize gene mutation in esophageal cancer and adjacent non-cancerous tissue and to study their roles in carcinogenesis.METHODS:Mutations of p53(exon 4-8) were analysed in 24 surgically resected human esophageal specimens from Linxien in Henan and 21 normal human esophagus maintained in the improved SCID(severe combined immunodeficient) mice treated or not with N-amyl-N-methylnitrosamine (AMN) by polymerase chain reaction (PCR) and single-strand conformation polymorphism(SSCP),and DNA sequencing.RESULTS:p53 gene mutations were predominantly detected in both esophageal cancer specimens(18 mutations) and adjacent non-cancerous tissues (10 mutations).G-A transition was predominant.Fourteen normal human esophagus continously treated with AMN induced cancerouschange(6 mutations),and G-A transition at codon 283 of p53 gene was detected in the lesion.CONCLUSIONS:The results suggest that p53 gene mutation is the same in esophageal cancer and adjacent non-cancerous tissues and environmental or endogenous nitrosamines may cause higher incidence of esophageal cancer at Linxian in He’nan,China.