【摘要】 目的研究片状核酸内切酶1(flap endonuclease 1,Fen1)基因多态性与多环芳烃(polycyclic aromatic hydrocarbons,PAHs)接触工人外周血淋巴细胞DNA损伤易感性的相关性。方法选取137名焦炉作业工人(接触组)和49名无职业性PAHs及射线接触的医务人员(对照组)作为调查对象。测定尿中1-羟基芘(urinary 1-hydroxypyrene,1-OHPyr)水平反映PAHs接触内剂量,用碱性彗星试验评价个体外周血淋巴细胞DNA损伤,采用聚合酶链反应-限制性片段长度多态性方法分析Fen1基因rs4246215和rs174538位点的多态性。结果在校正性别、年龄、每日吸烟量、焦炉作业工龄和尿1-OHPyr后,接触组Fen1基因rs4246215、rs174538位点多态性与彗星Olive尾矩的关联差异有统计学意义(P<0.05),其中,携带杂合子基因型的个体彗星Olive尾矩短于携带突变型纯合子的个体,差异有统计学意义(P<0.05);携带不同单体型的个体彗星Olive尾矩,差异有统计学意义(P<0.05),其中携带GG/TA+TG单体型对的个体彗星Olive尾矩短于携带TA/TA+TG单体型对的个体,差异有统计学意义(P<0.01)。非暴露组Fen1基因rs4246215、rs174538位点多态性和不同单体型与彗星Olive尾矩的关联无统计学意义(P>0.05)。结论 Fen1基因rs4246215、rs174538位点的多态性可能是影响PAHs接触工人外周血淋巴细胞DNA损伤水平的易感性因素之一。更多还原

【Abstract】 Objective To investigate the association of polymorphisms of flap endonuclease 1(Fen1)gene and DNA damage in peripheral blood lymphocytes among workers exposed to polycyclic aromatic hydrocarbons(PAHs).Methods 137 coke-oven workers exposed to PAHs and 49 unexposed medical staff were recruited.Urinary 1-hydroxypyrene(1-OHPyr)was measured as the internal dose of PAHs for all subjects.DNA damage in peripheral lymphocytes was measured by alkaline comet assay.Two single nucleotide polymorphisms(SNPs)in Fen1 gene,including rs4246215 and rs174538 were detected by polymerase chain reaction-restriction fragment length polymorphism.Results After adjusting the sex,age,cigarettes per day,coking history and urinary 1-OHPyr,multivariate analysis of covariance revealed that the polymorphisms of Fen1 gene at loci rs4246215 and rs174538 were related to the olive TM in PAH exposed workers(P<0.05),those carrying heterozygosis were significantly shorter than those of carrying mutation genotype at loci rs4246215 and rs174538 of Fen1 gene(P<0.05).The olive TM was significantly different with different haplotypes in PAH exposed workers(P<0.05),and the olive TM among the individuals carrying GG/TA+TG haplotype pairs was significantly shorter than those carrying TA/TA+TG haplotype pairs(P<0.01).But no significant association between the polymorphisms of Fen1 gene and the olive TM was observed in unexposed controls(P>0.05).Conclusions Results suggest that Fen1 at loci rs4246215 and rs174538 polymorphisms might influence the susceptibility of DNA damage in workers exposed to PAHs.更多还原