Effects of glutathione depletion by buthionine sulfoximine on radiosensitization by oxygen and misonidazole in vitro
Buthionine sulfoximine (BSO) has been used to deplete glutathione (GSH) in V79-379A cells in vitro, and the effect on the efficiency of oxygen and misonidazole (MISO) as radiosensitizers has been determined. Treatment with 50 or 500 ..mu..M BSO caused a rapid decline in GSH content to less than 5% of control values after 10 hr of exposure. Removal of BSO resulted in a rapid regeneration of GSH after 50 ..mu..M BSO, but little regeneration was observed over the subsequent 10-hr period after 500 ..mu..M. Cells irradiated in monolayer on glass had an oxygen enhancement ratio (OER) of 3.1. After 10-14 hr pretreatment with 50 ..mu..M BSO, washed cells were radiosensitized by GSH depletion at all oxygen tensions tested. The OER was reduced to 2.6, due to greater radiosensitization of hypoxic cells than aerated ones by GSH depletion. In similar experiments performed with MISO, an enhancement ratio of 2.0 could be achieved with 0.2 mM MISO in anoxic BSO-pretreated cells, compared to 2.7 mM MISO in non-BSO-treated cells. These apparent increases in radiosensitizer efficiency in GSH-depleted cells could be explained on the basis of radiosensitization of hypoxic cells by GSH depletion alone. These results are consistent with hypoxic cell radiosensitization by GSH depletion and by MISO or oxygen acting by separate mechanisms.
- Research Organization:
- Mount Vernon Hospital, Northwood, England
- OSTI ID:
- 5565481
- Journal Information:
- Radiat. Res.; (United States), Vol. 102:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CELL KILLING
RADIOINDUCTION
FIBROBLASTS
BIOLOGICAL RADIATION EFFECTS
GLUTATHIONE
RADIOSENSITIVITY EFFECTS
MISONIDAZOLE
OXYGEN
HAMSTERS
ORGANIC SULFUR COMPOUNDS
OXYGEN ENHANCEMENT RATIO
X RADIATION
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BIOLOGICAL EFFECTS
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
ELEMENTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IONIZING RADIATIONS
MAMMALS
NONMETALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIATION EFFECTS
RADIATIONS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIZERS
RODENTS
SOMATIC CELLS
VERTEBRATES
560121* - Radiation Effects on Cells- External Source- (-1987)