Enhancement by N-methylformamide of the effect of ionizing radiation on a human colon tumor xenografted in nude mice
Polar solvents, which induce differentiation in murine and human tumor cells, enhance the effect of ionizing radiation on cultured mouse mammary and human colon cancer cells. To determine whether this enhancement occurs in vivo, DLD-2 human colon carcinoma xenografts in nude mice were treated with combinations of 6 MV photon irradiation, the polar solvent N-methylformamide (NMF), or combinations of the two agents. Nude mice bearing 300-mg s.c. implants of DLD-2 tumors were treated i.p. with 150 mg NMF/kg daily for 19 days. Local tumor irradiations were administered as graded single doses or as fractionated doses, daily for 4 days, following the third NMF injection. The growth-inhibiting effect of the radiation treatment for both single dose and fractionation protocols was enhanced by the polar solvent. NMF alone increased the time required for a doubling of initial tumor volume by 1.7 days, compared to control tumors. Initial tumor volume doubling times compared to untreated controls were increased by 3.6 and 7.6 days by photon doses of 10.0 and 13.75 Gy, respectively, whereas NMF plus 10.0 or 13.75 Gy increased the DLD-2 regrowth delay time by 7.5 or 12.9 days. NMF caused essentially equivalent enhancements, whether split-dose schedules of 2.5 Gy daily for 4 days, and 3.44 Gy daily for 4 days, or single doses of 10.0 and 13.75 Gy were used; therefore, radiation enhancement was not due to effects on sublethal damage repair. The results support the use of NMF, currently in Phase 1-Phase 2 clinical trials, with radiation in the therapy of selected human neoplasms.
- Research Organization:
- Rhode Island Hospital, Providence
- OSTI ID:
- 5970567
- Journal Information:
- Cancer Res.; (United States), Vol. 44:11
- Country of Publication:
- United States
- Language:
- English
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CARCINOMAS
RADIOTHERAPY
FORMAMIDE
RADIOSENSITIVITY EFFECTS
LARGE INTESTINE
CELL DIFFERENTIATION
IN VIVO
IONIZING RADIATIONS
MAN
MICE
RADIATION DOSES
SYNERGISM
TRANSPLANTS
AMIDES
ANIMALS
BODY
DIGESTIVE SYSTEM
DISEASES
DOSES
GASTROINTESTINAL TRACT
INTESTINES
MAMMALS
MEDICINE
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PRIMATES
RADIATIONS
RADIOLOGY
RODENTS
THERAPY
VERTEBRATES
550603* - Medicine- External Radiation in Therapy- (1980-)