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The use of drugs which deplete intracellular glutathione in hypoxic cell radiosensitization

Journal Article · · Int. J. Radiat. Oncol., Biol. Phys.; (United States)
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Diethylmaleate (DEM) is a thiol-biding reagent with specificity toward glutathione. Treatment of chinese hamster ovary (CHO) cells in vitro with 2 x 10/sup -4/ M DEM for one hour results in a decrease in glutathione content to less than 5% of control, without cytotoxicity. This treatment results in dose-modifying sensitization to radiation under hypoxic conditions, with no effect on the shoulder of the radiation survival curve. No effect on the radiation sensitivity of oxygenated cells was seen. DEM pretreatment enhances the radiosensitization of hypoxic cells by misonidazole, as well. Similar results were obtained in vivo with EMT6 tumors in BALB/c mice. Analysis of DNA damage by the alkaline elution assay indicates that DEM enhances radiation-induced single-strand breaks, but does not significantly affect repair, while diamide and N-ethylmaleimide inhibit repair, in addition to enhancing radiation-induced single-strand breaks.

Research Organization:
Stanford Univ. School of Medicine, CA
OSTI ID:
6713764
Journal Information:
Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:3/4; ISSN IOBPD
Country of Publication:
United States
Language:
English

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Related Subjects

560114 -- Radiation Effects on Biochemicals-- In Animals-- (-1987)
560121 -- Radiation Effects on Cells-- External Source-- (-1987)
560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMAL CELLS
ANIMALS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
AZOLES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBOXYLIC ACIDS
CELL KILLING
CONNECTIVE TISSUE CELLS
DICARBOXYLIC ACIDS
DNA
DRUGS
EXPERIMENTAL NEOPLASMS
FIBROBLASTS
GLUTATHIONE
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IMIDES
IN VITRO
MALEIC ACID
MAMMALS
MICE
MISONIDAZOLE
NEM
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOINDUCTION
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RECOVERY
REPAIR
RODENTS
SOMATIC CELLS
STRAND BREAKS
SURVIVAL CURVES
VERTEBRATES