Effects of glutathione depletion by buthionine sulfoximine on radiosensitization by oxygen and misonidazole in vitro

Journal Article · Sat Jun 01 00:00:00 EDT 1985 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3576703· OSTI ID:5565481

Shrieve, D C; Denekamp, J; Minchinton, A I

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), Journal Name: Radiat. Res.; (United States) Vol. 102:3; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CELL KILLING
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
ELEMENTS
FIBROBLASTS
GLUTATHIONE
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IONIZING RADIATIONS
MAMMALS
MISONIDAZOLE
NONMETALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN
OXYGEN ENHANCEMENT RATIO
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RODENTS
SOMATIC CELLS
VERTEBRATES
X RADIATION