Arsenic exists widely in nature, and hundreds of arsenic minerals have been discovered. Although arsenic and its compounds are Class I carcinogen published by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO), they have been used in pesticides, herbicides, insecticides and many kinds of alloys in real life. Many studies have shown that exposure to arsenic and its compounds are closely related to the development of cardiovascular diseases (Chen et al., 2011), type 2 diabetes mellitus (Liu et al., 2021), metabolic disorders (He et al., 2022), skin cancer, liver cancer, lung cancer and other diseases.
Epidemiological studies have shown that the main routes of arsenic exposure include respiratory inhalation, food and water intake, and skin absorption. Arsenic is mainly metabolized in the liver and absorbed in the small intestine (Jomova et al., 2011), and its compounds are divided into inorganic arsenic (iAs) and organic arsenic. The toxicity of iAs is significantly higher than that of organic arsenic, so the toxicity of arsenic is mainly focused on iAs (Souza et al., 2016). The main metabolites of iAs in vivo are monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA). In particular, arsine acid is transformed into arsine acid under the action of arsine acid reductase, which is then methylated into MMA, and DMA is formed under the catalysis of reductase (Aposhian et al., 2004). Therefore, iAs, MMA and DMA are selected as the measurement indexes of arsenic in individual urine.
Oxidative stress is known to be one of the important pathogenesis of arsenism. Arsenic can directly damage DNA to break DNA, inhibit DNA repair, cause chromosomal aberrations, and finally induce genetic material damage. As a mitochondrial DNA molecular marker, Cytochrome b (Cytb) gene has a moderate evolutionary rate. A small gene fragment contains evolutionary genetic information from intraspecific, intergeneric and even interfamily, which is considered to be one of the credible molecular markers to solve the problems of taxonomy and systematic evolution. In this study, Cytb gene was introduced into the study of arsenic exposure damage for the first time, and the severity of individual genetic material damage caused by arsenic exposure was evaluated by detecting the DNA damage level of Cytb gene.
In recent years, it has been found that the toxicity of MMA and DMA is much higher than that of iAs. Therefore, understanding the methylation and valence of arsenic metabolites in human body is of great significance to the study of arsenic poisoning in population (Tokar et al., 2012). Some researchers have found that the metabolism of arsenic is affected by a variety of factors, such as individual characteristics, exposure situation, diet and living habits (Wei et al., 2018). However, some studies believe that these factors have no effect on arsenic methylation (Huang et al., 2008). Therefore, the research results on the influencing factors of arsenic methylation level are not consistent. Among them, oxidative DNA damage has been reported to be related to the level of arsenic methylation, and we will use population samples for re-detection in this study.
In addition, it's reported that the rs174538 polymorphism of Flap endonuclease 1 (FEN1) gene is associated with the risk of esophageal cancer and neurocytoma (Guan et al., 2022). Xeroderma pigmentosum group C (XPC) gene polymorphism is closely related to the occurrence and development of breast cancer (Wei et al., 2022), epithelial ovarian cancer (Zhao et al., 2018), cervical cancer (Datkhile et al., 2022), lung cancer (Minina et al., 2019), esophageal squamous cell carcinoma, cardiac adenocarcinoma, bladder cancer (Ahmed et al., 2018) and other cancers (Dai et al., 2019). Therefore, we will analyze the correlation between FEN1 and XPC gene polymorphisms and the DNA damage of Cytb gene caused by arsenic exposure in this study.
Therefore, it's hypothesized that arsenic exposure would cause DNA damage of Cytb gene, which is related to urinary arsenic level, FEN1, XPC gene polymorphism and arsenic methylation level.