TCRT December 2004

category image Volume 3
No. 6 (p 525-670)
December 2004
ISSN 1533-0338
Radiosensitizer

Radiosensitization of Murine Ehrlich Ascites Tumor by a Combination of 2-deoxy-D-Glucose and 6-Aminonicotinamide (p. 659-664)

Enhanced radiosensitizing effects of a combination of 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor and 6-aminonicotinamide (6-AN) an analogue of nicotinamide, which inhibits hexose monophosphate shunt (HMP) have been demonstrated in vitro. The purpose of the present studies is to investigate in vivo effects of this combination in Ehrlich ascites tumor (EAT) bearing mice. EAT tumor was grown in Swiss albino strain A mice. Treatment induced growth delay and tumor free animal survival were evaluated as parameters of radiation response. Focal irradiation of the tumor with a single fraction of 10 Gy induced a moderate delay in tumor growth but did not lead to complete regression of the tumor. Intravenous administration of either 6-AN or 2-DG immediately before irradiation enhanced radiation-induced growth delay with a cure rate of 45%. However, administration of a combination of 2-DG (2 g/kg b.wt.) and 6-AN (2 mg/kg b.wt.) immediately before irradiation led to complete regression of tumor in 80% animals resulting in survival of more than 300 days. A similar response (∼80%) was observed when 2-DG dose was reduced to 1 g/kg in combination with 6-AN. It is concluded that 6-AN enhances the radiosensitizing effects of 2-DG and the combination may have potential application in improving radiotherapy of tumors.

Key words: 2-deoxy-D-Glucose (2-DG), 6-aminonicotinamide (6-AN), Cure rate, Ehrlich Ascites Tumor (EAT).

R Varshney, Ph.D.1,a,*
S Gupta, Ph.D.1,2,a
B S Dwarakanath, Ph.D.1

1Institute of Nuclear Medicine & Allied Sciences
Brig S K Mazumdar Marg
Delhi-110 054, India
2Department of Radiation Medicine
University of Kentucky
Lexington, KY 40536 USA

aAuthors have contributed equally.

*rajeev@inmas.org

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