Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment

Carcinogenesis. 2001 Dec;22(12):1979-85. doi: 10.1093/carcin/22.12.1979.


Accumulating evidence suggests that HO-1 plays an important role in cellular protection against oxidant-mediated cell injury. Our previous studies on hyperbaric oxygen (HBO; i.e. exposure to pure oxygen under high ambient pressure) indicated clearly increased levels of HO-1 in lymphocytes of volunteers 24 h after HBO treatment (1 h at 1.5 bar). Experiments with the comet assay (alkaline single cell gel electrophoresis) revealed that the same cells were almost completely protected against the induction of DNA damage by a repeated exposure or in vitro treatment with H(2)O(2) 24 h after the first HBO. In order to further investigate the role of HO-1 in HBO-induced adaptive response, we now performed experiments with isolated human lymphocytes exposed to HBO in vitro (2 h at 3 bar). Our results show that also under cell culture conditions, lymphocytes exhibit an adaptive protection similar to that observed in our previous work with healthy human subjects. The time-course of HO-1 induction proceeds in parallel to the development of an adaptive protection against the induction of oxidative DNA damage. A comparable protection was not seen in V79 cells, indicating a specific difference between the two investigated cell systems. Treatment with the specific HO-1 inhibitor tin-mesoporphyrin IX (SnMP) led to a complete abrogation of HBO-induced adaptive protection in human lymphocytes. Our results indicate a functional involvement of HO-1 in the adaptive protection of human lymphocytes against the induction of oxidative DNA damage. The exact mechanism by which HO-1 contributes to an adaptive response remains to be elucidated.

MeSH terms

  • Adaptation, Physiological / drug effects
  • Animals
  • Blotting, Western
  • CHO Cells
  • Cell Line
  • Comet Assay
  • Cricetinae
  • DNA Damage / drug effects
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase-1
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hyperbaric Oxygenation*
  • Lymphocytes / drug effects*
  • Lymphocytes / enzymology*
  • Lymphocytes / metabolism
  • Membrane Proteins
  • Metalloporphyrins / pharmacology
  • Oxidative Stress / drug effects
  • Oxygen / administration & dosage
  • Oxygen / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors


  • Membrane Proteins
  • Metalloporphyrins
  • RNA, Messenger
  • tin mesoporphyrin
  • Hydrogen Peroxide
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Oxygen