Protection by S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation- and cyclophosphamide-induced attenuation in antitumor resistance. [Mice]
Studies were performed to investigate whether S-2-(3-amino-propylamino)ethylphosphorothioic acid (WR-2721) can protect antitumor immune rejection responses against the damaging effects of whole-body irradiation (WBI) and cyclophosphamide (CY). The ability of WR-2721 to protect against WBI -induced decreased radioresponse of solitary tumors was also investigated. All experiments were performed with an immunogenic fibrosarcoma syngeneic to C3Hf/ Kam mice. WR-2721 was given i.p. at a dose of 400 mg/kg 30 min before WBI with gamma-rays or CY injection. WBI with 650 rads reduced the number of tumor cells needed for tumor take in 50% of animals from 5.1 X 10(4) cells in normal mice to 2.0 X 10(2). WR-2721 given before WBI almost entirely abolished the effect of WBI : the number of tumor cells needed for tumor take in 50% of animals was 1.4 X 10(4). Treatment of mice with WBI or CY increased the number of tumor nodules in the lung generated by fibrosarcoma cells injected i.v. 5 days later, in a linear dose response. WR-2721 greatly reduced this metastasis enhancement effect of WBI and CY with protection factors of 2.5 for WBI and 1.8 for CY. Fibrosarcomas of 8 mm in diameter exhibited a decreased radiocurability when growing in WBI mice: the dose of irradiation yielding local tumor control in 50% of animals in these mice was 5950 compared to a dose of irradiation yielding local tumor control in 50% of animals of 4160 rads in normal mice. WR-2721 given before WBI inhibited this effect of WBI : the dose of irradiation yielding local tumor control in 50% of animals was 5210 rads. The proportion of macrophages in tumors growing in WBI mice was significantly reduced, but not when WR-2721 was first given. WR-2721 greatly reduced the damaging effects of WBI and CY on natural killer cell activity.
- Research Organization:
- Univ. of Texas, Houston
- OSTI ID:
- 6537141
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 44:6; ISSN CNREA
- 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.
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
CELL KILLING
CELL PROLIFERATION
COLONY FORMATION
CONNECTIVE TISSUE CELLS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROMAGNETIC RADIATION
EXPERIMENTAL NEOPLASMS
EXTERNAL IRRADIATION
FIBROSARCOMAS
GAMMA RADIATION
IMMUNE REACTIONS
IONIZING RADIATIONS
IRRADIATION
MACROPHAGES
MAMMALS
MEDICINE
METASTASES
MICE
NEOPLASMS
NUCLEAR MEDICINE
PHAGOCYTES
RADIATIONS
RADIOINDUCTION
RADIOLOGY
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOTHERAPY
RODENTS
SARCOMAS
SOMATIC CELLS
THERAPY
TUMOR CELLS
VERTEBRATES
WHOLE-BODY IRRADIATION