Influence of WR 2721 on the efficacy of radiotherapy and chemotherapy of murine tumors

Journal Article · Mon Mar 01 04:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90679-4· OSTI ID:6713643

Clement, J J; Johnson, R K

The effect of WR2721 on the response of tumors to radiation, antineoplastic alkylating drugs, and DNA binding agents was evaluated and compared to the degree of normal tissue protection provided by WR 2721 against these agents. WR 2721 administered to mice bearing P388 leukemia or Lewis lung carcinoma was found to reduce the radiosensitivity of the leukemia and lung tumor by dose modifying factors of 1.4 and 1.3, respectively. WR 2721 protected bone marow, intestine, and skin from radiation by factors of 1.9. 1.4 and 1.8. WR 2721 protected mice from the lethality of cyclophosphamide by a factor of only 1.2 whereas protection from melphalan toxicity was more dramatic with a dose modifying factor of 1.6. In chemotherapy studies of established M5076 ovarian tumor, the combination of WR 2721 plus cyclophosphamide was equivalent in activity to cyclophosphamide alone. WR 2721 did not modify the antitumor activity of melphalan in early Lewis lung carcinoma did not decrease the antileukemic effects of this agent by a factor of 2.6 indicating tumor protection greater than host protection in the leukemia. The antitumor activity of the DNA binding agents etoposide (VP16-213) and mitoxantrone against systemic P388 leukemia was not diminished by WR 2721, while a substantial increase in host toxicity was noted for the combinations. The protective effects of WR 2721 against radiation and drug damage were, therefore, not entirely selective for normal tissues. In some cases the degree of tumor protection can be similar to, or greater than, normal tissue protection.

• Research Organization: Arthur D. Little, Inc., Cambridge, MA
• OSTI ID: 6713643
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:3/4; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
ANIMAL TISSUES
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BODY
BONE MARROW
CHEMOTHERAPY
DIGESTIVE SYSTEM
DISEASES
DNA
DRUGS
ENDOXAN
EXPERIMENTAL NEOPLASMS
GASTROINTESTINAL TRACT
HEMATOPOIETIC SYSTEM
HEMIC DISEASES
IMMUNOSUPPRESSIVE DRUGS
INTESTINES
LEUKEMIA
LUNGS
MAMMALS
MEDICINE
MICE
NEOPLASMS
NUCLEAR MEDICINE
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RADIOLOGY
RADIOSENSITIVITY EFFECTS
RADIOTHERAPY
RESPIRATORY SYSTEM
RODENTS
SKIN
THERAPY
THIOIC ACIDS
TISSUES
VERTEBRATES