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Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans

Department of Pharmacology and Institute of Public Health, The Panum Institute, University of Copenhagen. Department of Neuroanaesthesia, The Neuroscience Center, Copenhagen University Hospital, DK-2200 Copenhagen N, Denmark

¹Correspondence: Institute of Public Health (c/o Department of Pharmacology), The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. E-mail: fipm{at}farmakol.ku.dk

The present study investigated the effect of a single bout of exhaustive exercise on the generation of DNA strand breaks and oxidative DNA damage under normal conditions and at high-altitude hypoxia (4559 meters for 3 days). Twelve healthy subjects performed a maximal bicycle exercise test; lymphocytes were isolated for analysis of DNA strand breaks and oxidatively altered nucleotides, detected by endonuclease III and formamidipyridine glycosylase (FPG) enzymes. Urine was collected for 24 h periods for analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage. Urinary excretion of 8-oxodG increased during the first day in altitude hypoxia, and there were more endonuclease III-sensitive sites on day 3 at high altitude. The subjects had more DNA strand breaks in altitude hypoxia than at sea level. The level of DNA strand breaks further increased immediately after exercise in altitude hypoxia. Exercise-induced generation of DNA strand breaks was not seen at sea level. In both environments, the level of FPG and endonuclease III-sensitive sites remained unchanged immediately after exercise. DNA strand breaks and oxidative DNA damage are probably produced by reactive oxygen species, generated by leakage of the mitochondrial respiration or during a hypoxia-induced inflammation. Furthermore, the presence of DNA strand breaks may play an important role in maintaining hypoxia-induced inflammation processes. Hypoxia seems to deplete the antioxidant system of its capacity to withstand oxidative stress produced by exhaustive exercise.—Møller, P., Loft, S., Lundby, C., Olsen, N. V. Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans.

Key Words: FPG • high-intensity exercise • ENDO III • reactive oxygen species

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