Role of thiols in cellular response to radiation and drugs. Symposium: thiols
- Case Western Reserve Univ. Medical School, Cleveland, OH
Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme. A GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellular capacity for its resynthesis. If resynthesis is blocked by buthionine-S,R-sulfoximine(BSO), the NPSH, including GSH, is depleted more rapidly, Cellular thiol depletion by diamide, N-ethylmaleimide, and BSO may render oxygenated cells more sensitive to radiation. These cells may or may not show a reduction in the oxygen enhancement ratio (OER). Human A549 lung carcinoma cells depleted of their NPSH either by prolonged culture or by BSO treatment do not show a reduced OER but do show increased aerobic responses to radiation. Other nitrocompounds, such as misonidazole, are activated under hypoxic conditions to radical intermediates. When cellular thiols are depleted peroxide is formed. Under hypoxic conditions thiols are depleted because metabolically reduced intermediates react with GSH instead of oxygen. Thiol depletion, under hypoxic conditions, may be the reason that misonidazole and other nitrocompounds show an extra enhancement ratio with hypoxic cells. Thiol depletion by DEM or BSO alters the radiation response of hypoxic cells to misonidazole. In conclusion, we propose an altered thiol model which includes a mechanism for thiol involvement in the aerobic radiation response of cells.
- OSTI ID:
- 5527659
- Journal Information:
- Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 95:3; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560121* -- Radiation Effects on Cells-- External Source-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BIOCHEMISTRY
BIOLOGICAL MODELS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CHEMISTRY
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IONIZING RADIATIONS
LUNGS
MAMMALS
MAN
MISONIDAZOLE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXYGEN ENHANCEMENT RATIO
PRIMATES
RADIATIONS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RECOVERY
REPAIR
RESPIRATORY SYSTEM
SOMATIC CELLS
SULFOXIDES
SURVIVAL CURVES
THIOLS
TUMOR CELLS
VERTEBRATES
X RADIATION