Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs☆
Introduction
Polycyclic aromatic hydrocarbons (PAHs) are the main carcinogenic components in coke oven emissions (COEs) as a wide range of human “Class I carcinogens” (Jeng et al., 2013). The levels of urinary hydroxyl metabolites of PAHs could effectively reflect the recent exposure levels, and urinary 1-hydroxypyrene (1-OHPYR) was used as a biomarker for monitoring occupational PAH exposure (Rossella et al., 2009). Long-term exposure to PAHs could ultimately lead to a variety of diseases and tumorigenesis through inducing oxidative stress, micronuclei, telomere damage and chromosomal aberrations (Moorthy et al., 2015). Our previous studies have shown that the workers exposed to COEs had a dose-dependent risk of DNA damage (Wang et al., 2019a; Yang et al., 2007).
Telomeres are located at the end of eukaryotic chromosomes and sensitive to exogenous compounds. Telomere dysfunction has been identified as the main mechanism underlying chromosomal instability in the development of human cancers (Rudolph et al., 2001). Thus, telomere length in peripheral blood leukocytes was expected to be a reliable effective biomarker in the carcinogenic process induced by the environmental toxicants.
Chromosomal damage could trigger the cGAS/STING signaling pathway. It has been shown that cGAS localization to micronucleus is caused by genomic instability, and its recognition of micronuclei could serve as a cellular innate immune surveillance mechanism that detected a range of neoplasia-inducing processes (Mackenzie et al., 2017). Studies have shown that telomere terminal fusion caused by telomere shortening, loss of telomere cap protein or loss of telomere viscosity was the mechanism underlying nucleoplasmic bridge formation (Murnane, 2012). And the fracture of the nucleoplasmic bridge may also be a mechanism of micronuclei formation (Fenech et al., 2011). In addition, an increasing line of studies have indicated that telomere damage was able to generate cytosolic DNA species, activate the cGAS/STING pathway and engage the autophagy machinery, which inhibited cell proliferation (Nassour et al., 2019). Single nucleotide polymorphism (SNP) refers to the single base variation at the genetic level, which could be used as a susceptible biomarker. Our previous studies have focused on the relationship between telomere damage and genetic polymorphisms of telomere-related protein genes and metabolic enzyme genes (Bin et al., 2011; Duan et al., 2019). Therefore, we hypothesized that genetic variations in the cGAS/STING might be involved in the regulation of telomere damage.
Therefore, this study was aimed to explore the relationship between dose-related telomere damage and the genetic polymorphisms of the cGAS/STING signaling pathway in the workers exposed to PAHs.
Section snippets
Study subjects
A total of 544 healthy workers—all exposed to COEs for at least one year in the coking plants located in the north of China—were recruited as the exposure group. They performed duties at different locations in the coking plants, including the oven top, oven side, oven bottom, crude benzene section and blower operation room. A total of 238 healthy participants were recruited as the control group from the same region who had no occupational exposure to PAHs and other toxicants. After signing the
Air PAHs concentrations at different locations of the ovens
In this study, three representative sampling sites were selected for the detection of sixteen PAHs in the environment. Among them, two samples collected from the bottom of the furnace were below the detection limit (2.6 × 10−10 mg/L) for the Naphthalene. All samples from the bottom, side and top of the furnace were below the detection limit (1.3 × 10−10 mg/L) for the Acenaphthylene. For the detection of Acenaphthene, all samples from the bottom of the furnace were under the detection limit
Discussion
PAHs are most common environmental pollutants produced by incomplete combustion of organic compounds. Some PAHs are reported to be carcinogenic. Among them, benzo(a) pyrene (B(a)P), environmental chemical carcinogen, was often regarded as the representative of PAHs (Ostrem Loss et al., 2019). The working environment in coke oven plants had the higher concentration than the non-working environments for the exposure to PAHs (Wang et al., 2019a). In this study, the concentrations of total PAHs
CRediT authorship contribution statement
Xiaoran Duan: Formal analysis, Writing - original draft. Yongli Yang: Data curation, Methodology. Sihua Wang: Data curation, Investigation. Xiaolei Feng: Data curation, Investigation. Tuanwei Wang: Data curation, Investigation. Pengpeng Wang: Data curation, Investigation. Mingcui Ding: Data curation, Investigation. Hui Zhang: Data curation, Investigation. Bin Liu: Data curation, Investigation. Wan Wei: Data curation, Writing - review & editing. Wu Yao: Data curation, Writing - review & editing.
Declaration of competing interest
The authors declare that they have no conflict of interest.
Acknowledgments
The authors express their gratitude to all the individuals who volunteered to participate in this study. We also thank the Programs for the National Natural Science Foundation of China (81872597) and Natural Science Foundation of Henan Province (U170410430).
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This paper has been recommended for acceptance by Wen Chen.