Survival curves of irradiated glutathione-deficient human fibroblasts: indication of a reduced enhancement of radiosensitivity by oxygen and misonidazole

Journal Article · Mon Mar 01 00:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90657-5· OSTI ID:6715136

Midander, J ^[1]; Deschavanne, P J; Malaise, E P; Revesz, L

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1. Karolinska Inst., Stockholm, Sweden

Fibroblasts derived from a patient with 5-oxoprolinuria are genetically deficient in glutathione synthetase. This deficiency causes a dramatic decrease in intracellular glutathione (GSH) level. The radiosensitivity of GSH deficient cells (GSH) was studied in vitro using colony forming ability as an endpoint. Cells with normal GSH level, obtained from the healthy brother of the patient, were used as controls. When irradiated in 95% air-5% CO/sub 2/, GSH/sup -/ cells are slightly but significantly more radiosensitive than GSH/sup +/ controls (dose modifying factor (DMF) of 1.2). When irradiated in argon, the survival curve of GSH/sup -/ cells indicates an oxygen enhancement ratio (OER) of 1.5 when compared to the curve obtained in oxic conditions. The OER of control cells in the same conditions is 2.9. In comparison to results obtained in air, 100% oxygen moderately increases the radiosensitivity of GSH/sup +/ cells (DMF 1,23), while it has a very low effect on GSH/sup -/ cells (DMF 1.06). These results suggest that intracellular GSH plays an essential protective role in hypoxia, its effect is reduced in air and practically disappears in 100% oxygen. When cells are incubated with 8 mM misonidazole 2 hours before irradiation, the drug has a much greater sensitizing effect on GSH/sup +/ cells (DMF 2.33) than on GSH/sup -/ cells (DMF 1.55). The results demonstrate that intracellular GSH level plays a major role in the response of hypoxic cells, irradiated either alone or in the presence of misonidazole.

• OSTI ID: 6715136
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 8:3/4
• Country of Publication: United States
• Language: English

Related Subjects

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