title: Role of glutathione in apoptosis induced by radiation as determined by 1H MR spectra of cultured tumor cells.
abstract: The relationship between apoptosis induced by gamma radiation and glutathione in cells of two human cancer cell lines, HeLa from cervix carcinoma and MCF-7 from mammary carcinoma, was examined. MCF-7 cells appeared to be more radioresistant than HeLa cells, and radiation-induced apoptosis, which was monitored by assessing phosphatidylserine externalization, was observed in HeLa cells but not in MCF-7 cells. Glutathione levels monitored by (1)H MRS were higher in MCF-7 cells than in HeLa cells, while the opposite was true for the free glu signals. MCF-7 cells became more radiosensitive when treated with 0.1 mM buthionine sulfoximine, which inhibits GSH synthesis through inactivation of gamma-glutamylcysteine synthetase, with the concomitant appearance of radiation-induced apoptosis. We can thus reasonably associate, at least in part, the resistance of MCF-7 cells to apoptosis with a high level of glutathione and probably with a high activity of gamma-glutamylcysteine synthetase. A late decrease in glutathione concentration after irradiation was observed in MCF-7 cells, but not in HeLa cells and to a lesser degree in buthionine sulfoximine-treated MCF-7 cells. This would indicate that the radiation-induced decrease in glutathione concentration is not related to the onset of apoptosis, but it is more likely related to glutathione consumption as a result of detoxification reactions.
authors.affiliation: Dipartimento di Tecnologie e Salute and INFN Gruppo Collegato Sanita', Roma, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Rosi
authors.forename: Sveva
authors.initials: S
authors.lastname: Grande
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Luciani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Palma
authors.forename: Claudio
authors.initials: C
authors.lastname: Giovannini
authors.forename: Laura
authors.initials: L
authors.lastname: Guidoni
authors.forename: Orazio
authors.initials: O
authors.lastname: Sapora
authors.forename: Vincenza
authors.initials: V
authors.lastname: Viti
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002457:Cell Extracts; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010472:Perchlorates / Q000494:pharmacology; D011522:Protons
chemical_list: D002457:Cell Extracts; D010472:Perchlorates; D011522:Protons; D019328:Buthionine Sulfoximine; D005978:Glutathione