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.
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Data availability
The datasets created and analyzed in the course of this study may be requested from the corresponding author under reasonable conditions.
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Acknowledgements
The authors express their heartfelt gratitude to the factory committee for granting access to the study population and to all participants for their voluntary involvement and cooperation.
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All authors were involved in the study's conceptualization and design, methodology, data collection, and formal analysis: Eman Mahmoud Khalifa, Marwa Abdelgawad, Rateba Said, and Mona Abdallah Ramadan. Laboratory analysis and investigation: Marwa Abdelgawad; Writing—original draft: Eman Mahmoud Khalifa; Writing—review and editing: Eman Mahmoud Khalifa, Rateba Said, and Mona Abdallah Ramadan. All authors reviewed, edited, and approved the final version of the manuscript.
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This study received prospective approval from the Research Ethics Committee at the Faculty of Medicine, Cairo University, Egypt (ethics reference: N-243-2024), prior to any participant contact. All procedures were conducted in full accordance with the ethical standards set forth in the 2013 revision of the Declaration of Helsinki. Each prospective participant was provided with a thorough explanation of the study's aims, procedures, potential risks, and benefits, following which written informed consent was secured before enrollment. Participant privacy was rigorously safeguarded at every stage of the investigation, encompassing sample collection, laboratory analysis, data coding, and results documentation. Participants were provided with copies of their serological test reports to facilitate any further clinical evaluation or therapeutic intervention.
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Khalifa, E.M., Abdelgwad, M., Mohammed, R.S. et al. Heat-induced genomic instability in the workplace: integrated assessment of oxidative stress burden and expression of DNA repair genes. Int Arch Occup Environ Health 99, 57 (2026). https://doi.org/10.1007/s00420-026-02242-2
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DOI: https://doi.org/10.1007/s00420-026-02242-2