Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment

Hyperbaric oxygen (HBO) treatment of human subjects (i.e. exposure to 100% oxygen at a pressure of 2.5 ATA for a total period of 3 x 20 min) caused cl ear and reproducible DNA damage in lymphocytes, as detected with the comet assay (single cell gel electrophoresis), Induction of DNA damage was found only after the first HBO exposure and not after further treatments of the s ame individuals, Furthermore, blood taken 24 h after HBO treatment was sign ificantly protected against the induction of DNA damage by hydrogen peroxid e (H2O2) in vitro, indicating that adaptation occurred due to induction of antioxidant defenses. The cells were not significantly protected against th e genotoxic effects of gamma -irradiation, suggesting increased scavenging of reactive oxygen species distant from nuclear DNA or an inducible change in the levels of free transition metals. We now demonstrate increased level s of heme oxygenase-1(HO-1) in lymphocytes 24 h after HBO treatment of volu nteers. Under the same conditions, superoxide dismutase, catalase and the D NA repair enzymes apurinic endonuclease and DNA polymerase beta were not en hanced in expression, We also show that protection against the induction of DNA damage by H2O2 in lymphocytes even occurs with a shortened HBO treatme nt which did not induce significant DNA damage by itself, Our results sugge st that increased sequestration of iron als a consequence of induced HO-1 m ight be involved in the adaptive protection after HBO treatment and that th e induction of DNA damage is not the trigger for adaptive protection.