Wang Tuanwei, Tu Yuting, Wang Kan, Gong Shiyang, Zhang Guanghui, Zhang Yunxia, Meng Yu, Wang Tongshuai, Li Anqi, Cui Junpeng, Liu Huan, Tang Weifeng, Xi Jing, Cao Yiyi, Luan Yang, Christiani David C, Au William, Xia Zhao-Lin
Department of Occupational Health & Toxicology, School of Public Health, Shanghai Medical College of Fudan University, 130 Dongan Road, Shanghai 200032, China.
Department of Occupational & Environmental Health, School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang 453003, Henan Province, China.
Environ Pollut. 2020 Nov 30;273:116181. doi: 10.1016/j.envpol.2020.116181.
Carcinogenic effects from low doses of lead (Pb) exposure to populations have been suspected but not concluded. Therefore, a large-scale cross-sectional study was conducted by us to investigate genotoxic effects from Pb exposure during 2016-2018 in North China. Blood lead levels (BLLs) and cumulative blood lead levels (CBLLs) were measured. Multiple relevant biomarkers were used to assess genotoxicity of Pb: mitochondrial DNA copy number (mtDNAcn, n = 871), Comet Tail Intensity (n = 872), γ-H2AX (n = 345), relative telomere length (rTL, n = 757), micronuclei (MN, n = 934) and phosphatidylinositol glycan class A mutation (PIG-A, n = 362). The BLL data show right-skewed distribution, with increase of the median (P, P) from 17.4 (8.9, 26.4) μg/dl in 2016 to 18.5 (10.5, 27.2) μg/dl in 2017, and to 20.8 (11.3, 31.0) μg/dl in 2018. Multivariate regression analyses show that mtDNAcn was non-linearly associated with BLLs or CBLLs, i.e. decreased at low levels but increased at the higher levels. Comet and Micronuclei data show positive dose-response relationships with BLLs as well as CBLLs. γ-H2AX data show an overall increased trend with BLLs while rTL data show a shortening trend. No associations were found for PIG-A mutation with Pb exposure. Our findings indicate that current low dose exposure to Pb can still cause health hazards to occupational populations, and the mechanism may be via the induction of DNA & chromosome damage rather than via the mutagenesis pathway.
低剂量铅（Pb）暴露人群的致癌作用已受到怀疑，但尚无定论。因此，我们开展了一项大规模横断面研究，以调查2016 - 2018年华北地区铅暴露的遗传毒性效应。测量了血铅水平（BLLs）和累积血铅水平（CBLLs）。使用多种相关生物标志物评估铅的遗传毒性：线粒体DNA拷贝数（mtDNAcn，n = 871）、彗星尾强度（n = 872）、γ-H2AX（n = 345）、相对端粒长度（rTL，n = 757）、微核（MN，n = 934）和磷脂酰肌醇聚糖A类突变（PIG-A，n = 362）。BLL数据呈右偏态分布，中位数（P，P）从2016年的17.4（8.9，26.4）μg/dl增加到2017年的18.5（10.5，27.2）μg/dl，再到2018年的20.8（11.3，31.0）μg/dl。多变量回归分析表明，mtDNAcn与BLLs或CBLLs呈非线性相关，即在低水平时降低，但在高水平时升高。彗星和微核数据显示与BLLs以及CBLLs呈正剂量反应关系。γ-H2AX数据显示随BLLs总体呈上升趋势，而rTL数据显示呈缩短趋势。未发现PIG-A突变与铅暴露有关。我们的研究结果表明，当前低剂量铅暴露仍可对职业人群造成健康危害，其机制可能是通过诱导DNA和染色体损伤，而非通过诱变途径。
