Heat-induced genomic instability in the workplace: integrated assessment of oxidative stress burden and expression of DNA repair genes.

Abstract

Objective: To elucidate the mechanistic pathways linking occupational heat exposure to adverse cellular outcomes among smelter workers and to quantify its effects on systemic oxidative stress biomarkers and the transcriptional modulation of genes controlling DNA repair and redox homeostasis.

Methods: This cross‑sectional study included 93 male workers from an aluminum production facility: 47 heat‑exposed employees and 46 administrative non-exposed personnel. Environmental monitoring was conducted using the Wet Bulb Globe Temperature (WBGT) index. Medical and occupational histories were captured via a structured questionnaire. Serum levels of malondialdehyde (MDA) and 8‑hydroxy‑2'‑deoxyguanosine (8‑OHdG), as well as the enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC), were determined. Expression of human NADPH oxidase‑1 (hNOX1), microRNA‑34a (miR‑34a), 8‑oxoguanine DNA glycosylase‑1 (OGG1), and sirtuin‑3 (SIRT3) was evaluated by quantitative RT‑PCR.

Results: WBGT levels in maintenance, forging, and furnace areas exceeded recommended threshold limit values. Compared with the control group, heat‑exposed subjects exhibited significantly elevated concentrations of both MDA and 8‑OHdG. Conversely, antioxidant parameters, namely SOD, GPx, and TAC, demonstrated statistically significant declines (p < 0.001). Furthermore, molecular analysis indicated a notable increase in hNOX1 and miR‑34a gene expression, while OGG1 and SIRT3 were significantly downregulated in exposed workers (p < 0.001). MDA showed a strong positive correlation with 8‑OHdG (p < 0.001), age (p = 0.009), and employment duration, whereas SIRT3 showed a weak positive correlation with OGG1 (p = 0.05).

Conclusion: Occupational heat exposure was associated with oxidative stress, DNA damage, and altered expression of DNA repair and redox‑regulatory genes, indicating compromised cellular defense mechanisms among smelter workers.