Telomere shortening associated with increased levels of oxidative stress in sulfur mustard-exposed Iranian veterans

Mutat Res Genet Toxicol Environ Mutagen. 2018 Oct:834:1-5. doi: 10.1016/j.mrgentox.2018.06.017. Epub 2018 Jun 20.

Abstract

Sulfur Mustard (SM) is the most widely used chemical weapon. It was used in World War 1 and in the more recent Iran-Iraq conflict. Genetic toxicity and DNA alkylation effects of SM in molecular and animal experiments are well documented. In this study, lymphocytic telomere lengths and serum levels of isoprostane F2α were measured using q-PCR and enzyme immunoassay-based methods in 40 Iranian veterans who had been exposed to SM between 1983-88 and 40 non-exposed healthy volunteers. The relative telomere length in SM-exposed individuals was found to be significantly shorter than the non-exposed individuals. In addition, the level of 8-isoprostane F2α was significantly higher in the SM-exposed group compared to controls. Oxidative stress can be caused by defective antioxidant responses following gene mutations or altered activities of antioxidant enzymes. Chronic respiratory diseases and infections may also increaseoxidative stress. The novel finding of this study was a the identification of 'premature ageing phenotype'. More specifically, telomere shortening which occurs naturally with aging is accelerated in SM-exposed individuals. Oxidative stress, mutations in DNA repair genes and epimutaions may be among the major mechanisms of telomere attrition. These findings may help for a novel therapeutic strategy by telomere elongation or for validation of an exposure biomarker for SM toxicity.

Keywords: Oxidative stress; Sulfur mustard; Telomere shortening.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Chemical Warfare Agents / adverse effects*
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Humans
  • Iran
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Mustard Gas / adverse effects*
  • Oxidative Stress*
  • Telomere Shortening*
  • Veterans / statistics & numerical data*

Substances

  • Chemical Warfare Agents
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Mustard Gas