Tumour metabolism and radioprotection of normal tissue in Balb/c and CBA mice
de Villiers, Neil Heinrich
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The steady state in a tumour rapidly changes with its growth and the subsequent deteriorating blood and nutrient supply. This adaptation in the steady state of the tumour is shown in the increased lactate dehydrogenase and acid phosphatase activity in the tumour during it's growth. These alterations in the tumour metabolism places an increased burden on the body to supply nutrient and to discard the waste products of the tumour. This is demonstrated at the macroscopic level by the decreasing body weight and food intake when the tumour burden increases, and also at the metabolic levels by the responses of certain glycolytic and Cori cycle enzymes. Furthermore three distinct stages were observed in the Cori cycle response to the influence of the tumour namely, a silent or preclinical stage, a hypermetabolic stage and a hypometabolic stage. Although the decreasing body weight cannot be directly linked to the process of gluconeogenesis, the onset of anorexia appeared to coincide with the end of the hypermetabolic stage and the beginning of the hypometabolic stage in gluconeogenesis. This clearly shows that the body's steady state is adversely affected by the presence of the tumour and that the conditions at the metabolic level seem to cause the anorexia. Furthermore, it is well known that the success of cancer therapies depends entirely on the effectiveness of the modality to kill the tumour cell and on the ability' of the host to absorb the damage caused by the modality without being destroyed in the process itself. The second part of this study demonstrates the radioprotective effects of ATP at all levels. It is clear from this work that ATP had a bigger influence in protecting the normal tissue than it had on the tumour tissue. This was demonstrated by the response of acid phosphatase (AP) and glucose-ó-phosphate dehydrogenase (G-6-PDH) in the tumour and testis. Furthermore, it would seem that ATP has a multifactorial interaction with the cell, two possible mechanisms of protection are indicated by these results. The first of these interactions is through the receptors of the cell to stimulate enhanced glycolysis, for higher energy production and thus repair. The second possibility is the interaction of ATP with the receptor of the cell to inhibit the production of free radicals and thus damage, as demonstrated by the response of G-6-PDH and AP.