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

Yiyi Cao; Jing Xi; Chuanxi Tang; Ziying Yang; Weiying Liu; Xinyue You; Nannan Feng; Xin Yu Zhang; Jingui Wu; Yingxin Yu; Yang Luan

doi:10.1186/s41021-021-00230-1

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

Genes Environ. 2021 Dec 9;43(1):54. doi: 10.1186/s41021-021-00230-1.

Authors

Yiyi Cao^#¹, Jing Xi^#¹, Chuanxi Tang², Ziying Yang^{3

4}, Weiying Liu¹, Xinyue You¹, Nannan Feng¹, Xin Yu Zhang¹, Jingui Wu², Yingxin Yu^{3

4}, Yang Luan⁵

Affiliations

¹ School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People's Republic of China.
² Center for Disease Control and Prevention of the Changning District of Shanghai, Shanghai, 200051, People's Republic of China.
³ Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China.
⁴ Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Key Laboratory of City Cluster Environmental Safety and Green Development, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China.
⁵ School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People's Republic of China. yluan@sjtu.edu.cn.

^# Contributed equally.

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 (P_2-OH-Flu = 0.032, r_2-OH-Flu = 0. 268; P_2-OH-Phe = 0.022, r_2-OH-Phe = 0.286; P_3-OH-Phe = 0.0312, r_3-OH-Phe = 0.270; P_4-OH-Phe = 0.018, r_4-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.

Keywords: Genotoxicity; Lymphocyte cytokinesis-block micronucleus test; PIG-A assay; Polycyclic aromatic hydrocarbons.

Abstract

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