DNA damage and telomere length shortening in the peripheral blood leukocytes of 20 years SM-exposed veterans

• Published in: International immunopharmacology 2018-08, Vol.61, p.37-44
• Main Authors: Behboudi, Hossein, Noureini, Sakineh Kazemi, Ghazanfari, Tooba, Ardestani, Sussan K.
• Format: Article
• Language: English
• Subjects: 8-Hydroxydeoxyguanosine; Alkylation; Antioxidants; Biomarkers; Cellular senescence; Chemical warfare; Cytotoxicity; Damage; Deoxyribonucleic acid; DNA; DNA damage; Exposure; Gene expression; Immune system; INK4a protein; Leukocytes; Lipids; Males; Mustard gas; OGG1 protein; Organic chemistry; Oxidative DNA damage; Oxidative stress; p16 Protein; Patients; Peripheral blood; Proteins; Reactive oxygen species; Senescence; Sulfur; Sulfur mustard; Toxicity; Veterans
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2018.05.008

Sulfur mustard (SM) is a vesicant chemical warfare agent, and a very potent alkylating agent. SM exerts its cytotoxicity via direct alkylation of biomacromolecules, and overproduction of reactive oxygen species (ROS). Previous studies have shown that SM-induced oxidative stress has adverse effects on antioxidant defense system, and damages lipids and proteins. The aim of this study was to investigate the effect of SM-induced oxidative stress on DNA damage, and cellular senescence in SM-exposed victims. For this purpose, MDA levels as a measure of oxidative stress in the serum, 8-oxo-dG content of the genomic DNA, and OGG1 expression as two biomarkers of oxidative DNA damage, as well as, telomere length, and p16INK4a expression as two biomarkers of cellular senescence were measured in the peripheral blood leukocytes of 215 males who were exposed to SM 20 to 25 years ago, and 53 unexposed healthy males as the control group. Our results indicated that the levels of 8-oxo-dG, and OGG1 mRNA expression were significantly higher in SM-exposed individuals. Furthermore, a significant increase in the expression of p16INK4a was observed in SM-exposed patients, and leukocyte telomere length (LTL) was also significantly shorter in severe/very severe cases of SM-exposed patients when compared with unexposed controls. In conclusion, our data indicate that oxidative DNA damage is higher in SM-exposed patients, and their immune system has subjected to cellular senescence. •Higher levels of serum MDA levels indicate increased lipid peroxidation and oxidative stress in SM-exposed patients.•8-Oxo-dG content of leukocytes genomic DNA is significantly higher in SM-exposed patients.•Leukocyte OGG1 mRNA expression increases significantly in SM-exposed patients.•Leukocyte telomere length is significantly shorter in sever/very severe cases of SM-exposed patients.•The level of leukocytes p16INK4a mRNA expression is significantly higher in SM-exposed patients.