Effects of 6-aminonicotinamide and 2-deoxy-D-glucose combination on the bioenergetics of perfused Ehrlich ascites tumour cells as monitored by <sup>31</sup>P-MR spectroscopy
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Title |
Effects of 6-aminonicotinamide and 2-deoxy-D-glucose combination on the bioenergetics of perfused Ehrlich ascites tumour cells as monitored by 31P-MR spectroscopy
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Creator |
Sharma, R K
Maitra, A Jain, V |
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Description |
307-312
The niacin antagonist, 6-aminonicotinamide (6-AN) is currently being evaluated in preclinical trials as a potential radiosensitizer.2-Deoxy-D-glucose, a glucose antimetabolite is another promising differential radiomodifier. In this paper we report the effects of these antimetabolites on changes in bioenergetics of perfused immobilised Ehrlich ascites tumour (EAT) cells to predict their usefulness in energy-linked modification of radiation response. 31P-MRS has been used to monitor cellular energetics as reflected in the ratio of β-phosphate of ATP to inorganic phosphate (β-ATP/Pi) and accumulation of 6- phosphogluconate/2-deoxy-D-glucose-6-phosphate in these cells. We have earlier shown that treatment with 2-DG results in a decrease in the energy profile of perfused EAT cells. Presence of 6-AN alone induces a progressive decrease in the β-ATP/Pi ratios. The impaired energy status observed after 6-AN treatment prompted us to probe its utility in potentiating the effects of 2-DG. The combination of 6-AN and 2-DG sharply reduces the signal attributed to β-ATP to the noise levels. There was no recovery in energy profile even upto 12 hr after perfusion with drug-free medium. Since metabolic depletion of ATP is known to inhibit the post-irradiation DNA repair processes and induce apoptotic cascade, the combination may be of considerable clinical importance for optimizing the efficacy and selectivity of tumour radiotherapy. |
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Date |
2013-07-16T09:03:52Z
2013-07-16T09:03:52Z 2000-10 |
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Type |
Article
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Identifier |
0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/19837 |
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Language |
en_US
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Rights |
CC Attribution-Noncommercial-No Derivative Works 2.5 India
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Publisher |
NISCAIR-CSIR, India
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Source |
IJBB Vol.37(5) [October 2000]
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