表观遗传调控的干扰是癌症的公认机制,但其对铅(Pb)相关毒性的作用尚未得到充分研究。我们旨在研究职业性铅暴露是否与微核(MN)频率相关,并进一步探讨表观遗传基因调控的中介作用。所有从中国酸蓄电池厂招募的铅暴露工人,检测血铅水平(BLL)和淋巴细胞MN频率.此外,七个基因的甲基化水平(Line-1,RASSF1A,在230名工人中检查了RUNX3,p16,CYP26C1,hMLH1,p15)。使用鲁棒泊松回归模型来研究BLL与MN频率之间的关联。中介分析用于探索特定DNA甲基化的中介作用。在总共677名参与者中,71%是男性,BLL中位数为229.1μg/L(P25=155.5,P75=319.3;范围为8.9至647.7μg/L),平均MN频率为2.5‰(SD=1.8‰;范围为0至9‰)。来自基础模型的结果,根据年龄调整,性别,和身体质量指数,结果表明,在BLL中,每增加100μg/L,MN频率将增加1.38(95%保密间隔:1.34,1.43)。使用分类的暴露变量分析,观察到MN频率的BLL剂量反应增加:2.74(2.13,3.51),3.43(2.73,4.32),4.41(3.89,5.01)至6.86(6.02,7.81)。中介分析表明,Line-1甲基化显着介导了BLL与MN频率相关的3.6%。职业性铅暴露以剂量-反应关系诱导MN频率。这种关联的一部分是由Line-1启动子甲基化介导的。
Perturbation of epigenetic regulation is a well-established mechanism for cancer but its role for lead (Pb)-associated toxicity has not been adequately investigated. We aimed to investigate whether occupational Pb exposure is associated with micronuclei (MN) frequency and to further explored the mediating roles of epigenetic gene regulation. All the Pb-exposed workers recruited from a Chinese acid battery factory, blood lead levels (BLLs) and MN frequency in lymphocytes were measured. In addition, methylation levels of seven genes (Line-1, RASSF1A, RUNX3, p16, CYP26C1, hMLH1, p15) were examined among 230 workers. Robust Poisson regression model was used to investigate the association between BLLs and MN frequency. Mediation analysis was used to explore the mediating role of specific DNA methylation. Among total 677 participants, 71% were male, median BLLs was 229.1 μg/L (P25 = 155.5, P75 = 319.3; ranged from 8.9 to 647.7 μg/L), mean MN frequency was 2.5‰ (SD = 1.8‰; ranged from 0 to 9‰). Results from base model, adjusted for age, sex, and body mass index, showed that MN frequency would increase 1.38 (95%confidential interval: 1.34, 1.43) per 100 μg/L increment in BLLs. Using categorized exposure variable analyses, a BLLs dose-response increase in MN frequency was observed: 2.74 (2.13, 3.51), 3.43 (2.73, 4.32), 4.41 (3.89, 5.01) to 6.86 (6.02, 7.81). Mediation analysis indicated that Line-1 methylation significantly mediated 3.6% of the association of BLLs with MN frequency. Occupational Pb exposure induces MN frequency in a dose-response relationship. Part of this association was mediated by Line-1 promotor methylation.