Modification of SR 2508 sensitization in hypoxic V79 cells by manipulation of glutathione levels
This series of experiments employed the hypoxic cell sensitizer SR 2508 in concentrations ranging from 0.1 to 10 mM and V-79 cells irradiated in air or made hypoxic in glass syringes, then irradiated with 15 MV X rays. Using a series of survival curves measured at the various concentrations, K curves relating sensitizer enhancement ratio (SER) to SR 2508 concentration were calculated with normal GSH levels or with depletion of GSH to 0% using 1 mM buthionine sulfoximine (BSO) or elevation to 200% of normal using 1 mM oxothiazolidine carboxylate (OTZ). Survival curves were fitted by computer, allowing calculation of standard errors for the SER values. The depletion of GSH by BSO sensitized hypoxic and aerated cells significantly and caused more than additive enhancement of SR 2508 sensitization in hypoxic cells. Elevation of GSH with OTZ protects cells irradiated in air or hypoxia and reduces the SER obtained with SR 2508. The results further support the importance of GSH levels in influencing sensitization by nitroimidazoles.
- OSTI ID:
- 6074153
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 16:5
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GLUTATHIONE
BIOSYNTHESIS
IMIDAZOLES
RADIOSENSITIVITY EFFECTS
ANOXIA
FIBROBLASTS
HAMSTERS
LUNGS
METHIONINE
OXYGEN
SURVIVAL CURVES
THIAZOLES
X RADIATION
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AZOLES
BODY
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
ELEMENTS
HETEROCYCLIC COMPOUNDS
IONIZING RADIATIONS
LIPOTROPIC FACTORS
MAMMALS
NONMETALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIATIONS
RADIOPROTECTIVE SUBSTANCES
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
SYNTHESIS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture