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

Carcinogenesis. 2000 Oct;21(10):1795-9. doi: 10.1093/carcin/21.10.1795.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology*
  • Adult
  • Carbon-Oxygen Lyases / biosynthesis
  • Catalase / biosynthesis
  • DNA Damage*
  • DNA Polymerase beta / biosynthesis
  • DNA Repair / physiology
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Deoxyribonuclease IV (Phage T4-Induced)
  • Enzyme Induction
  • Heme Oxygenase (Decyclizing) / biosynthesis*
  • Heme Oxygenase-1
  • Humans
  • Hydrogen Peroxide / toxicity
  • Hyperbaric Oxygenation*
  • Lymphocytes / drug effects
  • Lymphocytes / physiology
  • Membrane Proteins
  • Oxidative Stress / physiology*
  • Superoxide Dismutase / biosynthesis

Substances

  • Membrane Proteins
  • Hydrogen Peroxide
  • Catalase
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Superoxide Dismutase
  • DNA Polymerase beta
  • Deoxyribonuclease IV (Phage T4-Induced)
  • Carbon-Oxygen Lyases
  • DNA-(Apurinic or Apyrimidinic Site) Lyase