The role of thiols in cellular response to radiation and drugs
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. Some nitroheterocyclic radiosensitizing drugs also deplete cellular thiols under aerobic conditions. Such reactivity may be the reason that they show anomalous radiation sensitization (i.e., better than predicted on the basis of electron affinity). 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.
- Research Organization:
- Division of Radiation Biology, Case Western Reserve University Medical School, Cleveland, Ohio
- OSTI ID:
- 5502610
- Journal Information:
- Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 95:3; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Cellular glutathione depletion by diethyl maleate or buthionine sulfoximine: no effect of glutathione depletion on the oxygen enhancement ratio
Factors involved in depletion of glutathione from A549 human lung carcinoma cells: implications for radiotherapy. [Buthionine sulfoximine]
Related Subjects
560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
AMINO ACIDS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BIOSYNTHESIS
CARBOXYLIC ACIDS
CELL CULTURES
COENZYMES
CYSTEINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GLUTATHIONE
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
INHIBITION
MAMMALS
MAN
MEA
MISONIDAZOLE
NITRO COMPOUNDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
OXYGEN ENHANCEMENT RATIO
PEPTIDES
PEROXIDES
POLYPEPTIDES
PRIMATES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RODENTS
SYNTHESIS
THIOLS
VERTEBRATES