Glutathione requirement for the rejoining of radiation-induced DNA breaks in misonidazole-treated cells.
The role of glutathione (GSH) in the rejoining of radiation-induced single-strand DNA breaks (ssb) was studied in human fibroblast cultures sensitized to radiation by a 30 min treatment with 1 mM misonidazole (MISO). Hypoxically irradiated cells, deficient in GSH, either inherently, or due to a 16 h incubation with 1 mM buthionine sulphoximine (BSO), rejoined the breaks after MISO treatment at a lower rate and to a lesser extent than did GSH-proficient cells. Without MISO treatment, the hypoxically induced ssb were rejoined in the GSH-deficient cells as effectively as in the proficient cells. It is concluded that a large proportion of the breaks which arise after hypoxic irradiation in the presence of MISO are of a different type to those which arise in the absence of the drug, and require a particular GSH-dependent, enzymatic repair system. This requirement for rejoining in hypoxically irradiated, MISO-treated cells is similar to that seen earlier in MISO-untreated, oxically irradiated cells, and suggests that the ssb induced by radiation in the presence of MISO or oxygen are of a similar nature.
D019328:Buthionine Sulfoximine; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000502:physiology*; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D008920:Misonidazole / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D004277:DNA, Single-Stranded; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008920:Misonidazole; D004247:DNA; D005978:Glutathione