PIG-A gene mutation as a genotoxicity biomaker in polycyclic aromatic hydrocarbon-exposed barbecue workers.

IF 2.7 4区 医学 Q2 GENETICS & HEREDITY
Yiyi Cao, Jing Xi, Chuanxi Tang, Ziying Yang, Weiying Liu, Xinyue You, Nannan Feng, Xin Yu Zhang, Jingui Wu, Yingxin Yu, Yang Luan
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引用次数: 6

Abstract

Background: The PIG-A gene mutation assay is a valuable tool for measuring in vivo gene mutations in blood cells. The human PIG-A assay, used as a potential genotoxicity biomarker, is minimally invasive, sensitive, and cost-efficient; however, the relationship between carcinogen exposure and PIG-A mutations is not well understood.

Methods: We investigated the genotoxic effect of red blood cells using PIG-A assay and lymphocyte cytokinesis-block micronucleus test in barbecue restaurant workers (N = 70) exposed to polycyclic aromatic hydrocarbons (PAHs) and self-identified healthy control subjects (N = 56). Urinary PAH metabolites were measured to evaluate internal exposure levels.

Results: Multivariate Poisson regression showed that the PAH-exposed workers exhibited significantly higher PIG-A mutant frequency (MF) (8.04 ± 6.81 × 10- 6) than did the controls (5.56 ± 5.26 × 10- 6) (RR = 0.707, 95% CI: 0.615-0.812, P < 0.001). These results indicate that PAH exposure is a risk factor for elevated PIG-A MF. The frequencies of micronuclei (MN) and nuclear buds (NBUD) in the PAH-exposed workers (MN: 3.06 ± 2.07 ‰, NBUD: 1.38 ± 1.02 ‰) were also significantly higher than in the controls (MN: 1.46 ± 0.64 ‰, P < 0.001; NBUD: 0.70 ± 0.60 ‰, P < 0.001). Additionally, PIG-A MFs showed better associations with several urinary hydroxylated PAH metabolites (P2-OH-Flu = 0.032, r2-OH-Flu = 0. 268; P2-OH-Phe = 0.022, r2-OH-Phe = 0.286; P3-OH-Phe = 0.0312, r3-OH-Phe = 0.270; P4-OH-Phe = 0.018, r4-OH-Phe = 0.296), while the increase in MN, NPB, and NBUD frequencies was not associated with any OH-PAH metabolites; and high-PAH-exposed workers showed the highest PIG-A MFs. Furthermore, there was a significant association between PIG-A MF and PAH exposure levels (Chi-square test for trend, P = 0.006).

Conclusions: Our results indicate that an increase in PIG-A MF in barbecue workers could reflect the response to PAH exposure, providing evidence of its potential as a genotoxicity biomarker in human risk assessment.

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多环芳烃暴露烧烤工人中猪- a基因突变的遗传毒性生物标志物研究。
背景:猪- a基因突变试验是一种有价值的工具,用于测量体内基因突变的血细胞。作为潜在遗传毒性生物标志物的人猪- a测定具有微创性、敏感性和成本效益;然而,致癌物质暴露与猪- a突变之间的关系尚不清楚。方法:采用猪血红蛋白- a (PIG-A)测定和淋巴细胞分裂阻滞微核试验对暴露于多环芳烃(PAHs)的烧烤餐厅工作人员(N = 70)和自检健康对照(N = 56)红细胞的遗传毒性进行研究。测量尿液多环芳烃代谢物以评估内部暴露水平。结果:多变量泊松回归分析结果显示,多环多酚暴露工人猪- a突变频率(MF)(8.04±6.81 × 10- 6)显著高于对照组(5.56±5.26 × 10- 6) (RR = 0.707, 95% CI: 0.615 ~ 0.812, P 2-OH-Flu = 0.032, r2-OH-Flu = 0)。268;P2-OH-Phe = 0.022, r2-OH-Phe = 0.286;P3-OH-Phe = 0.0312, r3-OH-Phe = 0.270;P4-OH-Phe = 0.018, r4-OH-Phe = 0.296),而MN、NPB和NBUD频率的增加与OH-PAH代谢物无关;高多环芳烃暴露的工人表现出最高的猪- a MFs。此外,猪- a MF与多环芳烃暴露水平之间存在显著相关性(趋势的卡方检验,P = 0.006)。结论:我们的研究结果表明,烧烤工人中猪- a MF的增加可以反映对多环芳烃暴露的反应,为其作为人类风险评估的遗传毒性生物标志物的潜力提供了证据。
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来源期刊
Genes and Environment
Genes and Environment Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.00
自引率
0.00%
发文量
24
审稿时长
27 weeks
期刊介绍: Genes and Environment is an open access, peer-reviewed journal that aims to accelerate communications among global scientists working in the field of genes and environment. The journal publishes articles across a broad range of topics including environmental mutagenesis and carcinogenesis, environmental genomics and epigenetics, molecular epidemiology, genetic toxicology and regulatory sciences. Topics published in the journal include, but are not limited to, mutagenesis and anti-mutagenesis in bacteria; genotoxicity in mammalian somatic cells; genotoxicity in germ cells; replication and repair; DNA damage; metabolic activation and inactivation; water and air pollution; ROS, NO and photoactivation; pharmaceuticals and anticancer agents; radiation; endocrine disrupters; indirect mutagenesis; threshold; new techniques for environmental mutagenesis studies; DNA methylation (enzymatic); structure activity relationship; chemoprevention of cancer; regulatory science. Genetic toxicology including risk evaluation for human health, validation studies on testing methods and subjects of guidelines for regulation of chemicals are also within its scope.
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