DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure

Abstract

Delayed effects of sulfur mustard (SM) exposure on the levels of five important damage/repair proteins were investigated in 40 SM-exposed veterans of Iran-Iraq war and 35 unexposed controls. A major DNA damage biomarker protein - phosphorylated H2AX - along with four DNA repair proteins in cell response to the genome damage MRE11, NBS1, RAD51, and XPA were evaluated in blood lymphocytes from the veterans and controls using western blotting. Mean levels of XPA, MRE11, RAD51 and NBS1 were lower in SM-exposed patients and the decrease in NBS1 was significant. Even though the raised level of phosphor-H2AX in SM-poisoned group compared to the controls was not significant it was consistent with DNA damage findings confirming the severity of damage to the DNA after exposure to SM. There were correlations between the values of RAD51 and NBS1 proteins as well as XPA and MRE11 proteins. More than two decades after exposure to SM, there is still evidences of DNA damage as well as impaired repair mechanisms in cells of exposed individuals. Such disorders in cellular level may contribute to long term health problems of the SM veterans.

Current status of the acquired immune system of Iranian patients with long-term complications of sulfur mustard poisoning

“…Disorders in cellular level due to SM exposure may contribute to the observed prolonged health problems of these veterans. SM acts as DNA alkylating and hence as a genotoxic chemical, its cellular toxicity is mediated by covalent addition to guanine base of DNA [29,30]. SM is able to form adducts and cross-links in genome; consequently this genotoxicity and cellular impairment may be inherited via cells with excessive proliferation such as lymphocytes; in a way that lymphocytes might be deprived of the proper function.…”

Innate Immune System Status of Sulphur Mustard‐Poisoned Iranian Veterans Three Decades after Exposure

“…Genotoxicity of SM with the main mechanism of DNA cross‐linking has been well documented . The bone marrow progenitor cells which are committed to produce the cellular components of innate immunity have the potential of increased rate of proliferation and renewal.…”

“…Based on symptoms observed among the veterans, in addition to the possible mechanism of action of SM, the dysfunction of the immune system may be considered as a probable choice to be solved. Genotoxicity of SM with the main mechanism of DNA cross-linking has been well documented [7,11]. The bone marrow progenitor cells which are committed to produce the cellular components of innate immunity have the potential of increased rate of proliferation and renewal.…”

“…Furthermore, duration after exposure is a key feature that characterizes the effects of time on the integrity of human immune system. In other words, according to mutagenic effects of SM, time effect is so important on the progenitor cell lines producing immune cells . With reference to the common complications of SM poisoning which worsen over time, the hypothesis of immune dysfunction of veterans is critically justified.…”

Occupational Exposures and Environmental Health Hazards of Military Personnel

“…A study performed on 236 soldiers after 2–28 months from exposure showed complications affecting the respiratory tract in 78% of the cases, the central nervous system in 45%, the skin in 41%, eyes in 36%, and other effects at lower frequencies [ 17 ]. Other studies explored the long-term effects (after 15–20 years) of SM-exposure on Iranian veterans which demonstrated that the main complications were in lungs (42.5–100%), peripheral nerves (77–77.5%), eyes (39.3–77.61%), and skin (24.5–82.84%) [ 18 , 19 , 20 , 21 ]. High frequency variations found in these studies were due to differences in sample size (43 to 34,000 subjects analyzed), but nevertheless, the major pathological events were the same.…”