Influence of misonidazole, SR-2508, RSU-1069 and WR-2721 on spontaneous metastases in C57BL mice

Journal Article · Mon Feb 01 04:00:00 EST 1988 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(88)90438-5· OSTI ID:5297300

Kanclerz, A; Chapman, J D

The effect of treatments with the hypoxic cell radiosensitizers misonidazole (MISO), SR-2508, RSU-1069, and with the radioprotector WR-2721 on spontaneously disseminated Lewis lung carcinoma (LLC) and B16 melanoma (B16M) was investigated. Tumors were implanted into the tails of C57BL mice and were surgically removed after reaching volumes of approximately 40 mm3. This technique results in the induction of metastatic disease in lungs and at other anatomical sites and allows the independent treatment of disseminated tumor cells. The radiosensitizers and the radioprotector were administered 24 hr after surgery and animals were killed 14 and 30 days after removal of LLC and B16M, respectively. The time to death from spontaneous metastases was also measured. Both single treatments with large doses of MISO (1.0 g/kg) and fractionated therapy with smaller doses (0.5 g/kg on 5 consecutive days) promoted the formation of metastases to the lungs, lymph nodes and other organs. The survival times of MISO treated animals did not differ from control animals but manifestation of metastatic disease in the lungs and other organs occurred at earlier times. Administration of equitoxic doses of SR-2508 (3.0 g/kg) and RSU-1069 (0.1 g/kg) also promoted metastases formation. Mice treated with these radiosensitizers developed more metastases in the lungs and at other sites. Treatment with a single dose of WR-2721 (0.4 g/kg) promoted lung metastases but exerted a suppressive effect on lymph node tumors. When the radioprotector was given in fractionated schedules in three different doses (0.05 g/kg, 0.1 g/kg and 0.2 g/kg for 10 consecutive days) a slight enhancement of lung metastases and suppression of extrapulmonary metastases was observed.

• Research Organization: Univ. of Alberta, Edmonton (Canada)
• OSTI ID: 5297300
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 14:2; ISSN IOBPD
• Country of Publication: United States
• Language: English

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550603 -- Medicine-- External Radiation in Therapy-- (1980-)
560152* -- Radiation Effects on Animals-- Animals
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BODY
CARCINOMAS
COMPARATIVE EVALUATIONS
DISEASES
DRUGS
EXPERIMENTAL NEOPLASMS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
LUNGS
LYMPH NODES
LYMPHATIC SYSTEM
MAMMALS
MELANOMAS
METASTASES
MICE
MISONIDAZOLE
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RADIOSENSITIZERS
RESPIRATORY SYSTEM
RODENTS
VERTEBRATES