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

Journal Article · Mon Mar 01 04:00:00 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

---

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), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:3/4; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

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