Operating room professionals are constantly exposed to waste anesthetic gases (WAGs) due to the extensive use of inhalational anesthetics (NIOSH - National Institute for Occupational Safety and Health NIOSH, 2007). Consequently, WAGs stand out for their potential and controversial damage to genetic material and generation of reactive oxygen species (ROS), leading to cellular oxidative stress in occupationally exposed individuals, which may represent risks to the health of professionals (Rozgaj et al., 2009; Costa Paes et al., 2014; Souza et al., 2016; Szyfter et al., 2016; Aun et al., 2018; Braz et al., 2018, 2020a; Çakmak et al., 2019; Neghab et al., 2020; Hua et al., 2021).

Gene expression analysis allows early detection of changes in the profile of transcripts, helping to understand the cellular mechanisms used in response to exposure (Joseph, 2017). Similar to clinical studies, the expression of important genes has already been studied in surgical patients under inhaled anesthetics (Braz et al., 2011; Freire et al., 2018; Jafarzadeh et al., 2020; Arruda et al., 2021). However, to date, only two studies have evaluated the expression of some genes in professionals occupationally exposed to WAGs (Souza et al., 2021; Aun et al., 2023), which is a topic that has been little explored.

One of the great challenges in risk assessment facing occupational exposure is the genetic variability and consequent individual sensitivity of response during/after interaction with chemical agents (Dourson et al., 2013). In this context, only a few studies have reported associations of single nucleotide polymorphisms (SNPs) in metabolism genes with increased DNA damage in professionals exposed to WAGs (Mušák et al., 2009; Santovito et al., 2015; Kargar Shouroki et al., 2019; Khisroon et al., 2020). However, no study has evaluated polymorphisms in key genes related to oxidative and DNA damage repair and antioxidative status in professionals occupationally exposed to WAGs, showing a gap in knowledge in this field.

When lesions occur in the genome, repair pathways are activated; the recognition, catalysis and removal of oxidative DNA damage occurs through the base excision repair pathway (Beaver et al., 2018), whose initiator element consists of 8-oxoguanine DNA glycosylase 1 (OGG1) transcribed by the gene located in an important region by several polymorphism studies involving genetic instability and cancer (Goode et al., 2002; Mitra et al., 2011; Peng et al., 2014), whereas X-ray repair cross complementing 1 (XRCC1) encodes a protein with several domains capable of interacting with repair components of single-strand DNA breaks that form after exposure to ionization and alkylating agents (Abbotts and Wilson, 2016). The switch from serine to cytosine at position 326 of OGG1 (rs1052133) is associated with a reduction in enzymatic activity and genomic instability compared with the wild-type homozygote (Yamane et al., 2004; Hill and Evans, 2006), whereas it is believed that the glutamine variant in XRCC1 (rs25487) (-/Gln) may alter the interaction between the enzymatic components of the repair pathways, leading to susceptibility to genotoxicity (Ginsberg et al., 2011). In addition, the ATM gene encodes mutated ataxia-telangiectasia kinase (ATM), which plays roles in apoptotic and repair responses and in proteins involved in cell cycle checkpoints and regulatory pathways of the antioxidant response (Ditch and Paull, 2012; Cirotti et al., 2021). It is suggested that a polymorphism (rs600931) located in the noncoding region of ATM may influence the maturation process of mRNA and interfere with protein formation (Wang et al., 2009).

If there is inefficiency in the repair system, the structure and function of DNA can be affected, leading to genetic instability (micronucleus - MN and nuclear bud - NBUD as biomarkers of DNA damage) that can be detected in exfoliated oral cells, which are in direct contact with WAGs (Sommer et al., 2020). To effectively eliminate ROS through interaction with superoxide anions and conversion into hydrogen peroxide and oxygen, the superoxide dismutase (SOD) enzyme plays an important role in maintaining cellular homeostasis (Miao and St Clair, 2009). In relation to the SOD2 polymorphism (rs4880), the switch from valine to alanine at the 16th amino acid from the beginning of the signal sequence affects the conformation and consequent transport of SOD2 to the mitochondria (Duarte et al., 2016). The relationship between oxidative stress and DNA damage is well established; thus, the evaluation of oxidative stress (oxidant and antioxidant markers) is important as well as the assessment of the impact of SNPs and gene expression related to the repair of DNA damage and antioxidant status on these biomarkers concerning WAG exposure.

Therefore, this is the first study to evaluate possible pathways of WAG interaction in genes related to the repair/antioxidant response (OGG1/SOD2) through analyses of both gene expression and genetic susceptibility. In addition, other important gene polymorphisms (XRCC1 and ATM) were assessed; the influence of genetic susceptibility on cytogenetic and oxidative stress markers was assessed according to job occupation. Accounting for the possible consequences of occupational exposure to WAGs, our study attempted to contribute to a better understanding of the possible association between genetic susceptibility and gene expression with genetic instability and oxidative stress markers, further contributing to environmental medicine.