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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]

Journal Article · · Radiat. Res.; (United States)
DOI:https://doi.org/10.2307/3574841· OSTI ID:6586547
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In vitro studies with CHO cells indicate that the 2-nitroimidazole, misonidazole, is markedly more toxic under hypoxic conditions than under aerobic conditions. Also, survival curves determined using prolonged exposure to the drug under hypoxic conditions before irradiation have shown a reduction in the extrapolation number (tilde n) as well as the mean lethal dose (D/sub 0/). Studies with radioactive misonidazole have indicated that at 37/sup 0/C there is a gradual accumulation of radioactive material within hypoxic as compared to aerobic cells and that over an incubation period of 5 hr, a 2- to 3-fold increase in uptake by hypoxic cells is observed. Chromatographic analysis has shown that this increase in uptake is due to the accumulation of metabolites of misonidazole. It is suggested that both the increase in toxicity and reduction in tilde n as a result of prolonged incubation with misonidazole under hypoxic conditions are related to the formation of these metabolites.

Research Organization:
Ontario Cancer Inst., Toronto
OSTI ID:
6586547
Journal Information:
Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 75:3; ISSN RAREA
Country of Publication:
United States
Language:
English

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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
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL CULTURES
COBALT 60
COBALT ISOTOPES
DRUGS
ELECTROMAGNETIC RADIATION
GAMMA RADIATION
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IN VITRO
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
IRRADIATION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
METABOLITES
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIATIONS
RADIOISOTOPES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RESPONSE MODIFYING FACTORS
RODENTS
TOXICITY
VERTEBRATES
YEARS LIVING RADIOISOTOPES