• Jean J Latimer, Abdullah Alhamed, Stefanie Sveiven, Ali Almutairy, Nancy G Klimas, Maria Abreu, Kimberly Sullivan, and Stephen G Grant.
• Department of Pharmaceutical Sciences, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328.
• Mil Med. 2020 Feb 13; 185 (1-2): e47-e52.

IntroductionVeterans of the 1991 Gulf War were potentially exposed to a mixture of stress, chemicals and radiation that may have contributed to the persistent symptoms of Gulf War Illness (GWI). The genotoxic effects of some of these exposures are mediated by the DNA nucleotide excision repair (NER) pathway. We hypothesized that individuals with relatively low DNA repair capacity would suffer greater damage from cumulative genotoxic exposures, some of which would persist, causing ongoing problems.Materials And MethodsBlood samples were obtained from symptomatic Gulf War veterans and age-matched controls. The unscheduled DNA synthesis assay, a functional measurement of NER capacity, was performed on cultured lymphocytes, and lymphocyte mRNA was extracted and analyzed by sequencing.ResultsDespite our hypothesis that GWI would be associated with DNA repair deficiency, NER capacity in lymphocytes from affected GWI veterans actually exhibited a significantly elevated level of DNA repair (p = 0.016). Both total gene expression and NER gene expression successfully differentiated individuals with GWI from unaffected controls. The observed functional increase in DNA repair capacity was accompanied by an overexpression of genes in the NER pathway, as determined by RNA sequencing analysis.ConclusionWe suggest that the observed elevations in DNA repair capacity and NER gene expression are indicative of a "hormetic," i.e., induced or adaptive protective response to battlefield exposures. Normally such effects are short-term, but in these individuals this response has resulted in a long-term metabolic shift that may also be responsible for the persistent symptoms of GWI.© Association of Military Surgeons of the United States 2019.

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