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

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.