Dennog C, Hartmann A, Frey G, Speit G
Universität Ulm, Abteilung Medizinische Genetik, Germany.
Mutagenesis. 1996 Nov;11(6):605-9. doi: 10.1093/mutage/11.6.605.
Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a variety of conditions. However, exposure to high concentrations of oxygen is known to induce damage to cells, possibly due to an increased oxygen radical production. As reactive oxygen species also cause DNA damage, we investigated the DNA-damaging effect of HBO with the alkaline version of the single cell gel test (comet assay). Oxidative DNA base modifications were determined by converting oxidized DNA bases to strand breaks using bacterial formamidopyrimidine-DNA glycosylase (FPG), a DNA repair enzyme, which specifically nicks DNA at sites of 8-oxo-guanines and formamidopyrimidines. HBO treatment under therapeutic conditions clearly and reproducibly induced DNA damage in leukocytes of all test subjects investigated. Increased DNA damage was found immediately at the end of the treatment, while 24 h later, no effect was found. Using FPG protein we detected significant oxidative base damage after HBO treatment. DNA damage was detected only after the first treatment and not after further treatments under the same conditions, indicating an increase in antioxidant defences. DNA damage did not occur when the HBO treatment was started with a reduced treatment time which was then increased stepwise.
高压氧(HBO)疗法已成功用于多种病症的治疗。然而,已知暴露于高浓度氧气会导致细胞损伤,这可能是由于氧自由基产生增加所致。由于活性氧也会导致DNA损伤,我们使用单细胞凝胶试验(彗星试验)的碱性版本研究了HBO的DNA损伤作用。通过使用细菌甲酰胺嘧啶-DNA糖基化酶(FPG)(一种DNA修复酶)将氧化的DNA碱基转化为链断裂来测定氧化性DNA碱基修饰,该酶在8-氧代鸟嘌呤和甲酰胺嘧啶位点特异性切割DNA。在治疗条件下进行的HBO治疗在所有研究的受试对象的白细胞中均清晰且可重复地诱导了DNA损伤。在治疗结束时立即发现DNA损伤增加,而24小时后未发现影响。使用FPG蛋白,我们在HBO治疗后检测到了显著的氧化性碱基损伤。DNA损伤仅在首次治疗后检测到,在相同条件下进一步治疗后未检测到,这表明抗氧化防御能力增强。当以缩短的治疗时间开始HBO治疗,然后逐步增加治疗时间时,未发生DNA损伤。