Leng Shuguang, Cheng Juan, Pan Zufei, Huang Chuanfeng, Niu Yong, Dai Yufei, Li Bin, He Fengsheng, Zheng Yuxin
National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Biomarkers. 2004 Jul-Oct;9(4-5):395-406. doi: 10.1080/13547500400015618.
A wide variety of base damages and single-strand breaks formed by reactive oxygen species during metabolic activation of polycyclic aromatic hydrocarbons (PAHs) have been recognized to be involved in PAH carcinogenesis. In this study, alkaline comet assay was used to detect the DNA damage in peripheral blood lymphocytes among 143 coke-oven workers and 50 non-coke-oven workers, and the effects of genetic polymorphisms of XRCC1 and ERCC2 genes on DNA damage were evaluated. The olive tail moment was significantly higher in coke-oven workers than in non-coke-oven workers (2.6, 95% CI=2.1-3.3 versus 1.0, 95% CI=0.8-1.2, p<0.01), and significant correlation between ln-transformed urinary 1-OHP and ln-transformed olive tail moment was found in total population (n=193, Pearson's r=0.393, p<0.001) and in coke-oven workers (n=143, Pearson's r=0.224, p=0.007). The olive tail moment was significantly higher in coke-oven workers with GA genotype of G27466A polymorphism of XRCC1 than those with GG genotype (4.6, 95% CI=2.5-8.7 versus 2.4, 95% CI=1.9-2.9, p<0.01 with adjustment for covariates). No significant associations between C26304T, G28152A and G36189A polymorphisms of XRCC1 and G23591A and A35931C polymorphisms of ERCC2 and olive tail moment were found in both groups. The study showed that the alkaline comet assay is a suitable biomarker in the detection of DNA damage among coke-oven workers and it suggested that the A allele of G27466A polymorphism of XRCC1 may be associated with decreased DNA repair capacity toward PAH-induced base damage and strand breaks.
在多环芳烃(PAHs)代谢活化过程中,由活性氧形成的多种碱基损伤和单链断裂被认为与PAH致癌作用有关。在本研究中,采用碱性彗星试验检测了143名焦炉工人和50名非焦炉工人外周血淋巴细胞中的DNA损伤,并评估了XRCC1和ERCC2基因的遗传多态性对DNA损伤的影响。焦炉工人的橄榄尾矩显著高于非焦炉工人(2.6,95%CI=2.1-3.3对1.0,95%CI=0.8-1.2,p<0.01),并且在总人群(n=193,Pearson相关系数r=0.393,p<0.001)和焦炉工人(n=143,Pearson相关系数r=0.224,p=0.007)中发现ln转换后的尿1-OHP与ln转换后的橄榄尾矩之间存在显著相关性。XRCC1基因G27466A多态性为GA基因型的焦炉工人的橄榄尾矩显著高于GG基因型的工人(4.6,95%CI=2.5-8.7对2.4,95%CI=1.9-2.9,校正协变量后p<0.01)。在两组中均未发现XRCC1基因的C26304T、G28152A和G36189A多态性以及ERCC2基因的G23,591A和A35931C多态性与橄榄尾矩之间存在显著关联。该研究表明,碱性彗星试验是检测焦炉工人DNA损伤的合适生物标志物,并且提示XRCC1基因G27466A多态性的A等位基因可能与PAH诱导的碱基损伤和链断裂的DNA修复能力降低有关。