6533b85bfe1ef96bd12baa67

RESEARCH PRODUCT

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

Günter SpeitClaudia DennogUta EichhornAndreas RothfuβBernd Kaina

subject

AdultCancer ResearchDNA RepairDNA repairDNA damageCarbon-Oxygen LyasesBiologymedicine.disease_causeSuperoxide dismutasemedicineDNA-(Apurinic or Apyrimidinic Site) LyaseHumansLymphocytesDNA Polymerase betachemistry.chemical_classificationReactive oxygen speciesHyperbaric OxygenationSuperoxide DismutaseMembrane ProteinsGeneral MedicineHydrogen PeroxideCatalaseMolecular biologyDNA-(apurinic or apyrimidinic site) lyaseAdaptation PhysiologicalDeoxyribonuclease IV (Phage T4-Induced)Comet assayOxidative StresschemistryBiochemistryCatalaseEnzyme InductionHeme Oxygenase (Decyclizing)biology.proteinOxidative stressHeme Oxygenase-1DNA Damage

description

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 clear 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 same individuals. Furthermore, blood taken 24 h after HBO treatment was significantly protected against the induction of DNA damage by hydrogen peroxide (H(2)O(2)) in vitro, indicating that adaptation occurred due to induction of antioxidant defenses. The cells were not significantly protected against the 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 levels of heme oxygenase-1 (HO-1) in lymphocytes 24 h after HBO treatment of volunteers. Under the same conditions, superoxide dismutase, catalase and the DNA repair enzymes apurinic endonuclease and DNA polymerase beta were not enhanced in expression. We also show that protection against the induction of DNA damage by H(2)O(2) in lymphocytes even occurs with a shortened HBO treatment which did not induce significant DNA damage by itself. Our results suggest that increased sequestration of iron as a consequence of induced HO-1 might be involved in the adaptive protection after HBO treatment and that the induction of DNA damage is not the trigger for adaptive protection.

10.1093/carcin/21.10.1795https://pubmed.ncbi.nlm.nih.gov/11023535