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

The present study investigated the effect of a single bout of exhaustive ex ercise on the generation of DNA strand breaks and oxidative DNA damage unde r normal conditions and at high-altitude hypoxia (4559 meters for 3 days). Twelve healthy subjects performed a maximal bicycle exercise test; lymphocy tes were isolated for analysis of DNA strand breaks and oxidatively altered nucleotides, detected by endonuclease III and formamidipyridine glycosylas e (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 hy poxia, and there were more endonuclease III-sensitive sites on day 3 at hig h altitude. The subjects had more DNA strand breaks in altitude hypoxia tha n at sea level. The level of DNA strand breaks further increased immediatel y after exercise in altitude hypoxia, Exercise-induced generation of DNA st rand breaks was not seen at sea level. In both environments, the level of F PG and endonuclease III-sensitive sites remained unchanged immediately afte r exercise. DNA strand breaks and oxidative DNA damage are probably produce d by reactive oxygen species, generated by leakage of the mitochondrial res piration or during a hypoxia-induced inflammation, Furthermore, the presenc e of DNA strand breaks may play an important role in maintaining hypoxia-in duced inflammation processes. Hypoxia seems to deplete the antioxidant syst em of its capacity to withstand oxidative stress produced by exhaustive exe rcise.