Expression of telomere length and shelterin genes in men and women leukocytes and their correlations with lipid peroxidation in sulfur mustard gas intoxication

Sulfur mustard (SM), a chemical warfare agent, inflicts severe acute and chronic health effects. This study investigates the impact of SM-induced oxidative stress on telomere length (TL) and shelterin gene expression, which are crucial for telomere maintenance in exposed veterans. This study involved SM-exposed veterans and non-exposed controls. The SM-exposed group was divided into three subgroups based on exposure severity (severe, mild, and asymptomatic) and gender. Leukocyte TL, transcript of shelterin genes (TPP1, POT1, TIN2, TRF1, TRF2, RAP1), and plasma MDA were measured. TL was decreased in the SM-exposed group compared to the non-exposed group, while the MDA level was increased. The SM-exposed group showed lower expression of TIN2, TRF2, and the composite shelterin genes compared to the control group. In the SM-exposed subgroups, TL, TRF2 transcript, and composite shelterin gene expression were reduced compared to the non-exposed group, while the MDA levels were significantly increased. There are negative correlations between MDA and both TIN2/TRF2 expression and TL, and positive correlations between TL and composite shelterin gene expression. In the gender comparison, there were different effects of SM toxicity on TIN2, TPP1, TRF2, and the composite of shelterin gene expression between SM-exposed men and women. SM-exposed men had significantly higher MDA levels, while women showed no significant change. Also, there was no difference between non-exposed men and women. It is concluded that SM exposure increases lipid peroxidation, shortens telomeres, and alters shelterin genes in a gender-specific manner, suggesting accelerated biological aging as a delayed toxic effect.