Effect of tumor size on S-2-(3-aminopropylamino)ethylphosphorothioic acid and misonidazole alteration of tumor response to cyclophosphamide

Journal Article · Fri Jul 01 04:00:00 EDT 1983 · Cancer Res.; (United States)

OSTI ID:5346033

Milas, L; Ito, H; Hunter, N

The influence of tumor size on the ability of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) or misonidazole (MISO) to alter cyclophosphamide (CY) antitumor activity was investigated, using a chemically induced fibrosarcoma (FSA) and a spontaneous fibrosarcoma (NFSA) in C3Hf/Kam mice. Tumors were of two sizes at the time of treatment, 8-mm leg tumors and 4-day-old micrometastases in the lung. The antitumor activity of CY and its modification were assessed by growth delay of leg tumors and the reduction in the number of lung metastases. Both measures of tumor response were more pronounced as the dose of CY increased, and FSA was more sensitive to CY than was NFSA. WR-2721 (400 mg/kg), given 30 min before treatment with CY, reduced the effectiveness of CY on both FSA and NFSA. This reduction in effectiveness of CY was only minimal for leg tumors (dose-modifying factors were 1.1 for FSA and 1.03 for NFSA) but remarkable for lung micrometastases (dose-modifying factors were 1.81 for FSA and 1.55 for NFSA). Protection increased with the increase in the dose of WR-2721 and was also dependent on the time of injection relative to CY. The greatest protection occurred when WR-2721 was given within 30 min before to 15 min after CY. Tumor size had the opposite effect on MISO from that on WR-2721. MISO (1 mg/g) enhanced the effect of CY more effectively for leg tumors than for lung micrometastases: dose-modifying factors were 1.74 for FSA and 2.21 for NFSA growing in the leg and 1.27 for FSA and 1.11 for NFSA lung micrometastases. Therefore, tumor size appears to be a very important factor in determining the extent of WR-2721- and MISO-induced modification of CY antitumor effect.

• Research Organization: Department of Experimental Radiotherapy, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston
• OSTI ID: 5346033
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 43:7; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550600 -- Medicine
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BODY
BODY AREAS
CHEMOTHERAPY
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENDOXAN
EXPERIMENTAL NEOPLASMS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IMMUNOSUPPRESSIVE DRUGS
LEGS
LIMBS
LUNGS
MAMMALS
METASTASES
MICE
MISONIDAZOLE
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RADIOSENSITIZERS
RESPIRATORY SYSTEM
RESPONSE MODIFYING FACTORS
RODENTS
SIZE
THERAPY
VERTEBRATES