A rapid-mixing comparison of the mechanisms of radiosensitization by oxygen and misonidazole in CHO cells
Journal Article
·
· Radiat. Res.; (United States)
The mechanisms of hypoxic cell radiosensitization by oxygen and by the 2-nitroimidazole chemical sensitizer, misonidazole, were studied in CHO cells using rapid-mixing techniques. Both agents display a dose response of sensitivity in steady-state experiments which is satisfactorily fitted by a K function with maximum enhancement ratios (ER) of about 2.8. Rapid-mixing experiments demonstrated that oxygen sensitization in these cells is complete within about 10 msec even at concentrations as low as 2.6% oxygen, with no evidence for two time-resolved components as had been reported with V79 cells. Full sensitivity persists for at least 165 msec following an 8.4-fold dilution into hypoxic medium. No large temperature dependence was observed in the range 4 to 37/sup 0/C. Partial development of sensitization by misonidazole also occurs very quickly, within 25 msec with a 10mM drug concentration, but only to an ER of about 1.7, much below the level observed after many minutes incubation (approx.2.5) even at ice temperature. This development, too, has a very weak temperature dependence. It is suggested that although uptake of the drug is rapid, probably occurring by passive diffusion, an additional mechanism not involving gross metabolism and operating on the time scale of seconds to minutes is required to produce maximal sensitization in these cells.
- Research Organization:
- Univ. of Toronto, Canada
- OSTI ID:
- 5389386
- Journal Information:
- Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 90:1; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Studies on the toxicity and radiosensitizing ability of misonidazole under conditions of prolonged incubation. [Increased uptake, toxicity, and radiosensitizing effect in CHO cells under hypoxic conditions]
Interaction of misonidazole and oxygen in the radiosensitization of mammalian cells
Radiosensitizing and cytotoxic properties of ortho-substituted 4- and 5-nitroimidazoles: role of NPSH reactivity
Journal Article
·
Fri Sep 01 00:00:00 EDT 1978
· Radiat. Res.; (United States)
·
OSTI ID:6586547
Interaction of misonidazole and oxygen in the radiosensitization of mammalian cells
Journal Article
·
Thu May 01 00:00:00 EDT 1980
· Int. J. Radiat. Oncol., Biol. Phys.; (United States)
·
OSTI ID:6839327
Radiosensitizing and cytotoxic properties of ortho-substituted 4- and 5-nitroimidazoles: role of NPSH reactivity
Journal Article
·
Sun Feb 28 23:00:00 EST 1982
· Int. J. Radiat. Oncol., Biol. Phys.; (United States)
·
OSTI ID:6702914
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
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
COMPARATIVE EVALUATIONS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FEMALE GENITALS
GONADS
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
KINETICS
MAMMALS
MISONIDAZOLE
OPTIMIZATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OVARIES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
REACTION KINETICS
RODENTS
VERTEBRATES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
COMPARATIVE EVALUATIONS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FEMALE GENITALS
GONADS
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
KINETICS
MAMMALS
MISONIDAZOLE
OPTIMIZATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OVARIES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
REACTION KINETICS
RODENTS
VERTEBRATES