PIG-A gene mutation as a genotoxicity biomarker in human population studies: An investigation in lead-exposed workers
PIG-A gene mutation as a genotoxicity biomarker in human population studies: An investigation in lead-exposed workers
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PIG-A 基因突变作为人群研究中的基因毒性生物标志物：对铅暴露工人的调查。
DOI：
10.1002/em.22373
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发表时间：
2020-04-27
影响因子：
2.8
通讯作者：
Luan, Yang
中科院分区：
文献类型：
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作者：
Cao, Yiyi;Wang, Tuanwei;Luan, Yang
啮齿动物Pig-A基因突变试验在识别体内诱变物方面表现出了极高的敏感性，而人们对人类Pig-A试验用于风险评估的价值知之甚少。为了获得更多证据证明其作为预测致癌物暴露的生物标志物的潜力，我们调查了267名职业性铅暴露工人的PIG-A突变频率(MFS)，并进行了彗星试验和微核(MN)测试。多变量Poisson回归显示，铅接触工人的红细胞PIG-A总MFS(10.90+/-10.7×10(-6))显著高于我们先前研究的普通人群(5.25+/-3.6×10(-6))(p<；0.0001)。相反，用全血细胞彗星尾巴强度百分比来衡量，淋巴细胞微核率或DNA损伤没有增加。本年度工人血铅水平(接触生物标志物)升高(232.6+/-104.6微克/L，中位数：225.4微克/L)；累积血铅指数(CBLI)也根据当前和历史工人血铅数据计算。卡方检验显示，PIG-A MFS与CBLI显著相关(p=.0249)，但与当年BLL无关(p=.4276)。然而，彗星尾巴强度和MN频率与当年BLL的相关性要好于CBLI。本研究表明，PIG-A检测可作为检测铅暴露的遗传毒性效应的生物标志物，并证明一系列具有机制互补性的遗传毒性生物标志物可用于全面监测人类致癌风险。
The rodent Pig-a gene mutation assay has demonstrated remarkable sensitivity in identifying in vivo mutagens, while much less is known about the value of the human PIG-A assay for risk assessment. To obtain more evidence of its potential as a predictive biomarker for carcinogen exposure, we investigated PIG-A mutant frequencies (MFs), along with performing the Comet assay and micronucleus (MN) test, in 267 workers occupationally exposed to lead. Multivariate Poisson regression showed that total red blood cell PIG-A MFs were significantly higher in lead-exposed workers (10.90 +/- 10.7 x 10(-6)) than in a general population that we studied previously (5.25 +/- 3.6 x 10(-6)) (p < .0001). In contrast, there was no increase in lymphocyte MN frequency or in DNA damage as measured by percentage comet tail intensity in whole blood cells. Current year worker blood lead levels (BLL), an exposure biomarker, were elevated (232.6 +/- 104.6 mu g/L, median: 225.4 mu g/L); a cumulative blood lead index (CBLI) also was calculated based on a combination of current and historical worker BLL data. Chi-square testing indicated that PIG-A MFs were significantly related to CBLI (p = .0249), but independent of current year BLL (p = .4276). However, % comet tail intensity and MN frequencies were better associated with current year BLL than CBLI. This study indicates that the PIG-A assay could serve as biomarker to detect the genotoxic effects of lead exposure and demonstrates that a battery of genotoxicity biomarkers having mechanistic complementarity may be useful for comprehensively monitoring human carcinogenic risk.