Enhanced cytotoxicity of melphalan by prolonged exposure to nitroimidazoles: the role of endogenous thiols
Journal Article
·
· Int. J. Radiat. Oncol., Biol. Phys.; (United States)
The present study shows that a prolonged exposure of V-79 cells to a variety of nitroimidazoles (misonidazole, Ro-05-9963, Sr-2508, and MRT1-80) results in an enhanced cytotoxicity when these cells are subsequently exposed to melphalan. This process of enhanced malphalan toxicity occurred only when cells were pretreated with misonidazole under hypoxic conditions, suggesting that nitroreduction is necessary for chemosensitization as it is for increased radiosensitization. Different nitroimidazoles tested vary in the extent to which they sensitize cells to the subsequent action of melphalan. Repair from a misonidazole pretreatment is essentially complete by six hours. This study demonstrated that cysteamine could reduce the cytotoxicity of misonidazole and the enhancement of melphalan toxicity. This was an effect reversible with time and one implying similar mechanisms for the preincubation effect observed in vitro for radiation and chemotherapy agents.
- Research Organization:
- Coll. of Physicians and Surgeons of Columbia Univ., New York, NY
- OSTI ID:
- 6864714
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8; ISSN IOBPD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550200 -- Biochemistry
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.
AMINES
ANIMAL CELLS
ANOXIA
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
AZOLES
BIOCHEMISTRY
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHEMISTRY
CHEMOTHERAPY
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MEA
MISONIDAZOLE
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RECOVERY
REPAIR
SOMATIC CELLS
THERAPY
THIOLS
TOXICITY
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.
AMINES
ANIMAL CELLS
ANOXIA
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
AZOLES
BIOCHEMISTRY
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHEMISTRY
CHEMOTHERAPY
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MEA
MISONIDAZOLE
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RECOVERY
REPAIR
SOMATIC CELLS
THERAPY
THIOLS
TOXICITY