正常食管上皮和食管鳞状细胞癌组织中丙二醛-DNA加合物含量  

Detection of malondialdehyde-DNA adduct level by ^(32) P-postlabeling assay in normal human esophageal epithelium and esophageal squamous cell carcinoma

作　　者：邢德印[1] 宋南[1] 谭文[1] 林东昕[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所病因及癌变研究室,北京100021

出　　处：《中华肿瘤杂志》2001年第6期473-476,共4页Chinese Journal of Oncology

基　　金：国家杰出青年科学基金 ( 3982 5 12 2 ) ;国家"九五"医学科技攻关资助项目 ( 96 90 6 0 1 0 6 )

摘　　要：目的　研究正常食管上皮和食管癌组织中致癌性丙二醛 DNA加合物 (M1 dG)含量 ,探讨DNA氧化损伤与食管癌发生和发展的关系。方法　所有组织标本均来自食管癌高发区河南林县 ,32例正常食管上皮标本来源于组织活检 ,30例食管癌组织标本来源于外科手术切除的食管癌。DNA中M1 dG加合物含量以32 P 后标记方法测定。结果　在全部正常食管上皮和癌组织DNA中均检测到M1 dG加合物 ,但其含量 (中位数 )在正常食管上皮中为 3 .4/ 10 8核苷酸 (范围为 1.7/ 10 8～ 5 5 .4/ 10 8核苷酸 ) ,远低于食管癌组织的 14.1/ 10 8核苷酸 (范围为 1.4/ 10 8～ 5 9.0 / 10 8核苷酸 ) ,差异有极显著性(P <0 .0 0 0 1)。该加合物水平与受试者的性别、年龄、吸烟状态以及涉及酒精氧化产生自由基的细胞色素p45 0 2E1基因多态性无明显相关。结论　脂质过氧化产生的丙二醛对DNA的损伤可在食管上皮中累积 ,在癌组织中达相当高的水平 ,提示M1 dG加合物可能是导致食管癌发生和发展的重要因素。Objective To study whether the main malondialdehyde DNA adduct (M 1 dG) produced by lipid peroxidation is involved in the carcinogenesis of esophagus.Methods DNA samples were isolated from normal esophageal epithelium ( n =32) obtained by biopsy and esophageal squamous cell carcinoma specimens ( n =30) obtained by surgery. All tissue samples came from individuals living in Linxian, Henan, a high risk area of esophageal cancer. Contents of M 1 dG adducts were detected by 32 P postlabeling method.Results M 1 dG adducts were detectable both in the normal and cancerous tissue samples. However, normal esophageal epithelial tissues exhibited significantly lower levels of M 1 dG adducts (median 3.4, range 1.7/10 8 55.4/10 8 nucleotides) than those found in esophageal cancer tissues (median 14.1, range 1.4/10 8 59.0/10 8 nucleotides, P < 0.000 1). The adduct levels were neither associated with gender, age, tobacco smoking status or genetic polymorphism in the CYP2E1, an enzyme participating in the oxidation of ethanol to form reactive free radicals.Conclusions Our findings provide evidence that DNA damage, resulted from lipid peroxidation, can accumulate in the normal human esophageal tissue and reach relatively high level in cancer tissue which suggests that M 1 dG adducts may be involved in the initiation and progression of cancer with its mutagenic and carcinogenic effects. [

关 键 词：食管上皮 食管肿瘤 丙二醛 DNA加合物 食管鳞状细胞癌 

分 类 号：R735.1[医药卫生—肿瘤]