The rodent Pig‐a g ene 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 × 10⁻⁶) than in a general population that we studied previously (5.25 ± 3.6 × 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 μg/L, median: 225.4 μg/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.

中文翻译：

---

PIG-A基因突变在人群研究中作为遗传毒性生物标志物：一项对铅接触工人的调查。

啮齿动物的Pig-ag ene突变测定法在识别体内诱变剂方面显示出显着的敏感性，而对人类PIG-A测定法进行风险评估的价值知之甚少。为了获得更多证据证明其潜在的潜在致癌生物标志物，我们对267名职业接触铅的工人进行了PIG-A突变频率（MFs）以及彗星分析和微核（MN）测试的研究。多元Poisson回归显示，铅暴露工人的总红细胞PIG-A MFs（10.90±10.7×10 ^-6）显着高于我们先前研究的普通人群（5.25±3.6×10 ^-6）（p <.0001）。相反，以全血细胞中彗星尾巴强度的百分比来衡量，淋巴细胞的MN频率或DNA损伤没有增加。当年工人血铅水平（BLL）是一种暴露生物标志物，升高了（232.6±104.6μg/ L，中位数：225.4μg/ L）；还基于当前和历史工人BLL数据的组合计算了累计血铅指数（CBLI）。卡方检验表明，PIG-A MF与CBLI显着相关（p = .0249），但与当年BLL（p = .4276）无关。然而，与CBLI相比，％彗星尾巴强度和MN频率与当年BLL的关联更好。这项研究表明，PIG-A 该测定法可以用作检测铅暴露的遗传毒性作用的生物标志物，并证明具有机械互补性的一系列遗传毒性生物标志物可能对全面监测人类致癌风险有用。