吸烟者CYP1A1和GSTM1基因多态性与DNA损伤关系  

Study on Relationship between Smokers’ CYP1A1 and GSTM1 Gene Polymorphism and DNA Damage

作　　者：潘喜华[1] 仲伟鉴[1] 肖萍[1] 杨隽[1] 郑勇英[1] 郑卫东[1] 

机构地区：[1]上海市疾病预防控制中心,上海200336

出　　处：《环境与职业医学》2006年第3期211-213,242,共4页Journal of Environmental and Occupational Medicine

基　　金：上海市自然科学基金资助项目(编号:02ZB14088)

摘　　要：[目的]探讨吸烟者Ⅰ相代谢酶CYP1A1和Ⅱ相代谢酶GSTM1基因多态性与DNA损伤的关系。[方法]选择吸烟量、性别、年龄、生活方式基本相同的吸烟者123例,应用Pyrosequencing技术进行个体基因型测定,彗星试验测定外周血淋巴细胞DNA损伤程度。[结果]在123名吸烟者中,CYP1A1突变型(CYP1A1Val/Val)占CYP1A1等位基因型的28.5%,GSTM1缺失型(GSTM1null)占GSTM1等位基因型的56.1%。具有CYP1A1Val/Val和GSTM1null基因型的个体有19名,占吸烟者总数的15.4%。同时具CYP1A1突变型和GSTM1缺失型纯合个体,淋巴细胞的拖尾形成率为97.5%,尾长达120.9μm,尾矩为42.4μm,显著高于野生型个体(P<0.05),且尾部DNA的荧光强度明显升高,而突变杂合型个体DNA损伤无明显加重。[结论]CYP1A1突变型与GSTM1缺失型共同携带者对DNA损伤敏感,多个突变基因对DNA损伤可能具有协同作用。[ Objective ] To elucidate the relationship between DNA damage and smokers＇ transferase genetic polymorphism. [ Methods ] 123 subjects, which excluded potential confounding factors such as cigarette amount, sex, age, lifestyle etc., were recruited. The genotype CYP1A1 and GSTM1 were analyzed with Pyrosequencing technique and DNA damage of periphery blood lymphocyte was detected by alkaline comet assay. [ Results ] The frequency of CYP1A1 Val/Val genotype was 28.5% in CYP1A1 allele and GSTM1 null genotype was 56.1% of GSTM1 allele. 19 individualswith CYP1A1 Val/Val and GSTM1 null genotype were 15.4% of all subjects. The degree of DNA damage for periphery blood lymphocyte associated strongly with those individuals with homozygous mutation genotype of CYP1A1 and deletion of GSTM1. The tail ratio of periphery blood lymphocyte for homozygous mutation genotype was 97.5% （ tail length was 120.9 μm; tail moment was 42.4 μm ）, and was significantly higher than wild genotype control group （ P 〈 0.05 ）, intensity of tail DNAalso higher. No obvious damage was observed in heterozygous genotype subjects. [ Conclusion ] Study suggests that individuals with homozygous mutation genotype are genetic susceptibility to DNA damage caused by smoking, and mutation genotype as CYP1A1 Val/Val and GSTM1 null might have synergetic effects on DNA damage.

关 键 词：基因多态性 CYP1A1基因 GSTM1基因 彗星试验 

分 类 号：Q786[生物学—分子生物学]