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 · Fri Sep 01 00:00:00 EDT 1978 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3574841· OSTI ID:6586547

Wong, T W; Whitmore, G F; Gulyas, S

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), Vol. 75:3
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
RADIOSENSITIVITY
IMIDAZOLES
RADIOSENSITIVITY EFFECTS
TOXICITY
ORGANIC NITROGEN COMPOUNDS
ANOXIA
CELL CULTURES
COBALT 60
GAMMA RADIATION
HAMSTERS
IN VITRO
IRRADIATION
METABOLITES
RADIOSENSITIZERS
ANIMALS
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
COBALT ISOTOPES
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
RADIATIONS
RADIOISOTOPES
RESPONSE MODIFYING FACTORS
RODENTS
VERTEBRATES
YEARS LIVING RADIOISOTOPES
560121* - Radiation Effects on Cells- External Source- (-1987)