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.

journal_name

Radiat Res

journal_title

Radiation research

authors

Rosi A,Grande S,Luciani AM,Palma A,Giovannini C,Guidoni L,Sapora O,Viti V

doi

10.1667/RR0578.1

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

268-82

issue

3

eissn

0033-7587

issn

1938-5404

pii

RR0578

journal_volume

167

pub_type

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