Introduction

Any physician who is active in the field of hyperbaric medicine is well aware of the beneficial effects of hyperbaric oxygen in a broad variety of

injuries and pathophysiological states. On the other side it is well recognized that high oxygen levels may have deleterious effects on the lungs (Lorrain-Smith-effect) and the central nervous system (Paul-Bert-effect)1, as outlined in another chapter of this book.

The detrimental effects of exposure to high concentrations of oxygen are due to the abundance of oxygen free radicals1-3. Free radicals are defined as chemical species that possess one or more unpaired electrons. The term 'Reactive Oxygen Species' (ROS) collectively describes free radicals such as O2", OH^and other non-radical oxygen derivatives such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl)23. Unstable free radical species attack cellular components, causing damage to lipids, proteins and DNA1,2,4-7, which in turn can initiate a chain of events that may damage mammalian cells. Enhanced formation of oxygen free radical levels in the blood as a result of HBO exposure was demonstrated by electron spin resonance (ESR) spectroscopy8,9. Increased free radical formation in the body is likely to increase damage, in particular when antioxidant defences are insufficient, a situation generally termed "oxidative stress"2,10,11. Among other cellular targets the genome is particularly vulnerable11.

Oxidative DNA damage may consist of strand breaks, abasic sites, "alkali-labile sites" and oxidized bases6,7,11,12. Furthermore, ROS-induced DNA damage can lead to mutations, if lesions are not adequately repaired. If these relate to critical genes such as oncogenes or tumor suppressor genes, initiation and/or progression of cancer may result13,14. There has been concern about a cancer-causing or cancer-promoting effect of HBO, but a review of the scientific literature showed that the vast majority of published studies failed to demonstrate such an effect15-17. One of the mechanisms of a putative carcinogenic effect of HBO is the above-mentioned induction of DNA damage as a consequence of oxidative stress. Scarce data was only available until very recently the DNA-damaging potential of HBO has been thoroughly characterised using sensitive genotoxicity tests.

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