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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxic effects of ionizing radiation and elevated O2 levels (hyperoxia) are both thought to be mediated by oxidizing free radicals. In view of the reported hypersensitivity of ataxia telangiectasia (A-T) cells to the clastogenic effect of ionizing radiation, the chromosomal sensitivity of A-T cells to hyperoxic culture conditions was investigated in unirradiated and G0-irradiated A-T lymphocyte cultures. Unlike Fanconi's anaemia lymphocytes, which tend to respond to oxygen, especially after treatment with mitomycin C, both non-irradiated and G0-irradiated A-T lymphocytes failed to show an effect. We conclude that the excessive spontaneous and radiation-induced chromosomal breakage in A-T does not result from a deficiency in the cellular defences against the clastogenic effect of hyperoxia.
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PMID:Oxygen toxicity and chromosomal breakage in ataxia telangiectasia. 243 71

Fanconi's anaemia (FA) is characterized by increased spontaneous and induced chromosome fragility. This has been widely regarded to be due to a defect in DNA crosslink repair, because of the sensitivity of cells to known DNA crosslinking agents such as mitomycin C (MMC) and diepoxybutane (DEB). Although Fanconi cells are also sensitive to molecular oxygen, and may be protected by antioxidants, this has generally been considered to be a secondary phenomenon. However, it has recently been demonstrated that the FAC protein, coded for by the Fanconi anaemia gene for complementation group C, is strictly cytoplasmic and does not enter the nucleus even after DNA damage, which seems inconsistent with a role in DNA repair. We have studied the effects of MMC and oxygen on apoptotic cell death in FA group C (FA-C) and normal lymphoblastoid cell lines. Hyperoxia alone failed to induce apoptosis in either FA-C or normal cells. At ambient oxygen, MMC is known to generate oxygen free radicals, whereas decreased oxygen tension facilitates the metabolic activation of MMC for DNA crosslinking. We therefore studied the effects of MMC at 20% and 5% oxygen to favour oxygen radical generation or DNA crosslinking respectively. FA-C cells showed increased sensitivity compared to normal cells for the induction of apoptosis by MMC at 20% oxygen. When cells were treated with MMC at 5% oxygen we found no increased sensitivity of Fanconi cells to MMC when compared to normal cells. These results imply a role for oxygen free radicals, but not for DNA crosslinking, in the sensitivity of FA cells to MMC.
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PMID:The sensitivity of Fanconi anaemia group C cells to apoptosis induced by mitomycin C is due to oxygen radical generation, not DNA crosslinking. 902 6