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

• Published in: Toxicology letters Vol. 293; pp. 67 - 72
• Main Authors: Khateri, Shahriar, Balali-Mood, Mahdi, Blain, Peter, Williams, Faith, Jowsey, Paul, Soroush, Mohammad Reza, Behravan, Effat, Sadeghi, Mahmood
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2018
• Subjects: Adult; Age of Onset; Chemical Warfare; Chemical Warfare Agents - toxicity; Cross-Sectional Studies; Damage/repair proteins; DNA Damage; DNA Repair Enzymes - metabolism; Humans; Iran; Lung Diseases - chemically induced; Lung Diseases - metabolism; Lymphocytes - drug effects; Lymphocytes - metabolism; Male; Middle Aged; Monocytes - metabolism; Mustard Gas - toxicity; Smoking - adverse effects; Sulfur mustard; Veterans; Western blotting; PBS; Veterans; DNA damage; Sulfur mustard; MRN; PARP-1; Western blotting; NAD; DSB; CHK2; CHK1; γH2AX; SM; GAPDH; GSH; Damage/repair proteins; COPD
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2017.12.001

•Even 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.•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.•There were correlations between the values of RAD51 and NBS1 proteins as well as XPA and MRE11 proteins. However, none had significant correlation with years passed after exposure. 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.