Factors involved in depletion of glutathione from A549 human lung carcinoma cells: implications for radiotherapy. [Buthionine sulfoximine]

Conference · Wed Aug 01 04:00:00 EDT 1984 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

OSTI ID:6408324

Biaglow, J E; Varnes, M E; Epp, E R; Clark, E P

The rate of GSH resynthesis has been measured in plateau phase cultures of A549 human lung carcinoma cells subjected to a fresh medium change. Buthionine sulfoximine (BSO) blocks this resynthesis. Diethyl maleate (DEM) causes a decrease in accumulation of GSH. If DEM is added concurrently with BSO there is a rapid decline in GSH that is maximal in the presence of 0.5 mM DEM. GSH depletion rapidly occurs when BSO is added to log phase cultures which initially are higher in GSH content. Twenty-four hr treatment of A549 cells with BSO results in cells that are more radiosensitive in air and show a slight hypoxic radiation response. A 2 hr treatment with DEM results in some hypoxic sensitization and little increase in the aerobic radiation response. Cells treated simultaneously with BSO + DEM show little increase in the hypoxic radiation response, compared to DEM alone, but are more sensitive under aerobic conditions. Decreased cell survival for aerobically irradiated log phase A549 cells occurs within minutes after addition of a mixture of BSO + DEM. The authors suggest that the enhanced aerobic radiation response is related to an inability of GSH depleted cells to inactivate either peroxy radicals or hydroperoxides that may be produced during irradiation of BSO treated cells. Furthermore, enhancement of the aerobic radiation response may be useful in vivo if normal tissue responses are not also increased.

• Research Organization: Case Western Reserve Univ., Cleveland, OH
• OSTI ID: 6408324
• Report Number(s): CONF-8311204-
• Conference Information: Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Journal Volume: 10:8
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOCHEMISTRY
BIOSYNTHESIS
BODY
CARBOXYLIC ACIDS
CARCINOMAS
CELL KILLING
CHEMISTRY
DICARBOXYLIC ACIDS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
GLUTATHIONE
IMINES
IONIZING RADIATIONS
LUNGS
MALEIC ACID
MEDICINE
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDES
POLYPEPTIDES
PROTEINS
RADIATIONS
RADIOINDUCTION
RADIOLOGY
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOTHERAPY
RESPIRATORY SYSTEM
SURVIVAL CURVES
SYNTHESIS
THERAPY
THIOLS
TRANSFERASES
TUMOR CELLS
X RADIATION