Experimental evaluation of the glucose antimetabolite, 2-deoxy-D-glucose (2-DG) as a possible adjuvant to radiotherapy of tumors: I. Kinetics of growth and survival of ehrlich ascites tumor cells (EATC) in vitro and of growth of solid tumors after 2-DG and x-irradiation
- Gesellschaft fur Strahlen- und Umeltforschung mbH., Munchen, West Germany
Modifications of cell proliferation and survival induced by 2-DG and X-irradiation alone or in combination were studied under both aerobic and hypoxic conditions and for cells both in exponential and plateau phase. The degree of inhibition of cell proliferation was found to be dependent on absorbed dose of X rays and on the 2-DG/Glucose Molar ratio in the medium. At an equimolar ratio (2-DG/Glucose = 1) in nutrient medium the growth of euoxic EATC was ihibited by 80% relative to the control (without 2-DG). This inhibition was fully reversible up to 48 hours of the culture inoculation if 2-DG was removed from the medium, demonstrating the importance of glucose and glycolysis for tumor growth. The inhibitory effects of 2-DG on the viability of cultured cells when applied alone or in combination with radiation was found to be more pronounced in hypoxic cells than in euoxic cells. The combined effect of both noxae (2-DG and X-irradiation) on the growth inhibition of euoxic EATC in cultures was slightly more than additive, while they were clearly snyergistic on the growth inhibition of solid tumors in vivo. As tumors are known to have a fraction of hypoxic cells, it seems likely that synergistic action of 2-DG results from the stronger effect of 2-DG on these cells. The reason for the stronger effect may be a result of inhibition of their glycolytic energy supply limiting repair processes. Our results suggest that 2-DG could be used to advantage as an adjuvant in radiotherapy of human tumors.
- OSTI ID:
- 6704165
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 8:3/4
- Country of Publication:
- United States
- Language:
- English
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CELL PROLIFERATION
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ALDEHYDES
ANOXIA
ANTIMETABOLITES
ASCITES TUMOR CELLS
EHRLICH ASCITES TUMOR
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RADIOTHERAPY
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560152* - Radiation Effects on Animals- Animals
560121 - Radiation Effects on Cells- External Source- (-1987)