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目的研究核苷酸剪切修复酶基因多态性与焦炉作业工人外周血淋巴细胞染色体损伤易感性的关系。方法以140名焦炉作业工人(暴露组)和66名医务人员(对照组)作为研究对象,测定尿中1羟-基芘浓度反映多环芳烃暴露内剂量,用双核淋巴细胞微核评价个体外周血淋巴细胞染色体损伤,采用聚合酶链-限制性片段长度多态性方法分析ERCC1、ERCC2、ERCC4、ERCC5、ERCC6基因多态性,多元统计方法分析不同基因型与染色体损伤水平的关系。结果在校正年龄、性别、mEH基因型、自然对数转换后的尿1羟-基芘水平后,暴露组中ERCC1基因19007位点CC基因型个体微核率[(1.05±0.68)%]显著高于CT基因型[(0.81±0.66)%](P=0.01),或TT[(0.66±0.37)%](P=0.05),或CT+TT基因型个体[(0.75±0.63)%](P=0.004)。ERCC6基因3368位点AA基因型个体微核率[(1.00±0.69)%]显著高于AG[(0.67±0.42)%](P=0.05),或AG+GG基因型个体[(0.66±0.41)%](P=0.02)。进一步按焦炉工年龄均数(39.1岁)分层,发现在高年龄组ERCC1 C19007T和ERCC6 A3368G位点多态性与染色体损伤水平相关联;另外,高年龄组中ERCC2 G23591A位点GA基因型个体微核率[(1.40±0.63)%]高于GG基因型个体[(0.98±0.59)%](P=0.01)。结论ERCC1 C19007T、ERCC6 A3368G以及ERCC2 G23591A位点的多态性能够影响职业性多环芳烃暴露导致的外周血淋巴细胞染色体损伤水平。
OBJECTIVE: To study the relationship between the polymorphism of DNA repair gene and susceptibility to chromosome damage of peripheral blood lymphocytes in coke oven workers. Methods One hundred and forty coke oven workers (exposed group) and 66 medical workers (control group) were included in the study. The concentrations of 1-hydroxy-pyrene in the urine were measured to reflect the internal dose of PAH exposure. Individuals were evaluated with binuclear lymphocyte micronuclei The chromosomal damage of peripheral blood lymphocytes was analyzed. The polymorphisms of ERCC1, ERCC2, ERCC4, ERCC5 and ERCC6 were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The relationship between different genotypes and chromosomal damage was analyzed by multivariate statistical analysis. Results After adjusting for age, sex, mEH genotype, and urine 1-hydroxy-pyrene level after conversion to natural logarithmic phase, the frequency of micronuclei in CC genotype of ERCC1 gene 19007 in the exposed group [(1.05 ± 0.68)%] was significant Were significantly higher than that of the CT genotype [(0.81 ± 0.66)%] (P = 0.01) or TT (0.66 ± 0.37)%] (P = 0.05) (P = 0.004). The frequency of micronuclei in genotype AA of genotype 3368 of ERCC6 gene was significantly higher than that of AG [(0.67 ± 0.42)%] (P 0. 05) or AG genotype (0.66 ± 0.41 )%] (P = 0.02). Further stratification according to the average age of coke oven workers (39.1 years) stratified, found in the high age group ERCC1 C19007T and ERCC6 A3368G locus polymorphism associated with chromosome damage; In addition, high age group ERCC2 G23591A GA genotype Individual micronucleus rate [(1.40 ± 0.63)%] was higher than that of individuals with GG genotype [(0.98 ± 0.59)%] (P = 0.01). Conclusion The polymorphisms of ERCC1 C19007T, ERCC6 A3368G and ERCC2 G23591A can affect the chromosome damage of peripheral blood lymphocytes induced by occupational PAHs exposure.