In vivo investigation of the radiosensitization of metastases by nitroimidazoles. [Misonidazole; metronidazole; mice]
After the surgical removal of a primary Lewis lung tumor transplant from the flank of C57 B1 mice, the metastases occurring in the lung were later used to investigate the action of nitroimidazole compounds as possible radiosensitizers. This system resembles the commonest clinical problem, the presence of potentially lethal metastases after excision of the primary. The left mouse lung was x-irradiated: the right lung acted as a reference. The response measured was the ratio of the summed diameters of metastases per gram lung wt, left/right. This parameter had an approximately log. normal distribution and a satisfactory coefficient of variation in control series of mice. Using 1200 to 2400 rad of x irradiation, misonidazole (Ro-07-0582), a 2-nitroimidazole compound was found to have a radiosensitizing effect on metastases. The difference in the response of the left lung to x irradiation in the absence or presence of the drug was highly statistically significant and showed that a dose of 1.0 mg/g-body wt of the drug increased the effective dose of irradiation by approximately 50%. Metronidazole (Flagyl) a 5-nitro-imidazole compound, used as a single dose, did not enhance the action of 1200 or 2400 rad. Either drug used alone as a single dose was without effect on the size of the metastases. Reasons for the efficacy of Ro-07-0582 compared to Flagyl are discussed and the higher electron-affinity of the 2-nitroimidazole compound is stressed.
- Research Organization:
- Mill Hill Labs., London
- OSTI ID:
- 6585619
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 4:9/10; ISSN IOBPD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMALS
AZOLES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
COMPARATIVE EVALUATIONS
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIDAZOLES
IONIZING RADIATIONS
IRRADIATION
LOCAL IRRADIATION
LUNGS
MAMMALS
MEDICINE
METASTASES
METRONIDAZOLE
MICE
NITRO COMPOUNDS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RADIATION EFFECTS
RADIATIONS
RADIOLOGY
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RADIOTHERAPY
RESPIRATORY SYSTEM
RESPONSE MODIFYING FACTORS
RODENTS
THERAPY
VERTEBRATES
X RADIATION