Cellular glutathione depletion by diethyl maleate or buthionine sulfoximine: no effect of glutathione depletion on the oxygen enhancement ratio

Journal Article · Mon Oct 31 23:00:00 EST 1983 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3576226· OSTI ID:5011130

Mitchell, J B ^[1]; Russo, A; Biaglow, J E; McPherson, S

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1. National Institutes of Health, Bethesda, MD

The hypoxic and euoxic radiation response for Chinese hamster lung and A549 human lung carcinoma cells was obtained under conditions where their nonprotein thiols, consisting primarily of glutathione (GSH), were depleted by different mechanisms. The GSH conjugating reagent diethylmaleate (DEM) was compared to DL-buthionine-S,R-sulfoximine (BSO), an inhibitor of glutathionine biosynthesis. Each reagent depleted cellular GSH to less than 5% of control values. A 2-h exposure to 0.5 mM DEM or a 4- or 24-h exposure to BSO at 10 or 1 mM, respectively, depleted cellular GSH to less than 5% of control values. Both agents sensitized cells irradiated under air or hypoxic conditions. When GSH levels are lowered to < 5% by both agents, hypoxic DEM-treated cells exhibited slightly greater x-ray sensitization than hypoxic BSO-treated cells. The aerobic and anoxic sensitization of the cells results in the OER's of 2.8 and 3.0 for the DEM- and BSO-treated cells compared to 2.9 for the V79 control A549. BSO-treated cells showed an OER of 3.3 versus 3 for the control. Our results suggest that GSH depletion by either BSO or DEM sensitizes aerobic cells to radiation but does not appreciably alter the OER.

• OSTI ID: 5011130
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 96:2; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560121* -- Radiation Effects on Cells-- External Source-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOCHEMISTRY
BODY
CARBOXYLIC ACIDS
CELL KILLING
CHEMISTRY
DICARBOXYLIC ACIDS
DRUGS
ELECTROMAGNETIC RADIATION
GLUTATHIONE
HAMSTERS
IMINES
IONIZING RADIATIONS
LUNGS
MALEIC ACID
MAMMALS
MAN
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN ENHANCEMENT RATIO
PEPTIDES
POLYPEPTIDES
PRIMATES
PROTEINS
RADIATIONS
RADIOINDUCTION
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RESPIRATORY SYSTEM
RODENTS
SURVIVAL CURVES
TUMOR CELLS
VERTEBRATES
X RADIATION