Cytocidal and radiosensitizing properties of two newly developed nitroimidazole drugs: Ro 03-8799 RSU-1164

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1988

OSTI ID:5225261

Lakkis, M M

The cytocidal and radiosensitizing effects of two newly developed 2-nitroimidazole derivatives (Ro 03-8799 and RSU-1164) were evaluated with the original compound, misonidazole, serving as a reference agent. More specifically, euoxic and hypoxic BP-8 murine sarcoma cells were exposed for up to 3 hours to various concentrations of the three nitroimidazole derivatives, with or without irradiation, and the resulting cell lethality was monitored with the {sup 125}IUdR prelabeling assay. When cell death was evaluated as a function of drug molarity, the three nitroimidazoles displayed widely different toxicities, but when expressed in terms of toxicity ratio between euoxic and hypoxic cells, all three drugs showed nearly identical toxicity differentials of 16 to 18 in 1 hour drug incubation experiments. Prolonging the treatment period to 3 hours with RSU-1164, the toxicity ratio was increased significantly from 16 to 73. This increase was attributed to the bifunctional action of RSU-1164 as a combined electron-affinic and alkylating agent, with the alkylation component of hypoxic cell killing becoming more pronounced after prolonged drug incubation. Combined administration of hyperthermia and nitroimidazoles increased drug-induced cell lethality for all three agents, but did not materially change the relative toxicity differential between euoxic and hypoxic cells.

• Research Organization: Florida Agricultural and Mechanical Univ., Tallahassee, FL (USA)
• OSTI ID: 5225261
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
BETA DECAY RADIOISOTOPES
CELL KILLING
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVALUATION
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IRRADIATION
ISOTOPES
MAMMALS
MICE
MISONIDAZOLE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOISOTOPES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RODENTS
TOXICITY
TUMOR CELLS
VERTEBRATES