DEPLETION OF HIGH-ENERGY PHOSPHATE-COMPOUNDS IN THE TUMOR-BEARING STATE AND REVERSAL AFTER TUMOR RESECTION

Background. Cancer cachexia is a syndrome manifested by a variety of m etabolic abnormalities that include depletion of host energy stores. W e studied liver and skeletal muscle high energy phosphate compounds, i norganic phosphorus (Pi), and the energy charge in tumor-bearing (TB), pair fed non-tumor-bearing (NTB), and tumor-bearing resected (RES) ra ts. Methods. F344 rats were randomized into TB (n = 13), NTB (n = 13), and RES (n = 5) groups. On day 0, the flanks of the TB and RES animal s were injected with 1 x 10(7) methylcholanthrene (MCA)-induced sarcom a cells. On day 19, TB and NTB rat liver and skeletal muscle were anal yzed for adenine nucleotides, phosphocreatine, and Pi, and RES animals underwent tumor resection followed by tissue analysis 10 days later. Results. Although the liver adenylate energy charge was maintained, th e level of liver adenosine monophosphate was significantly increased a nd the liver adenosine diphosphate level was decreased in the TB anima ls (3.55 +/- 0.6, 3.70 +/- 0.3 mu moles/gm dry weight, p < 0.05, p = 0 .05, respectively) when compared with the NTB animals (3.06 +/- 0.4, 4 .00 +/- 0.5 mu mole/gm dry weight, p < 0.05). In addition, muscle aden osine triphosphate, phosphocreatine, and phosphocreatine/adenosine tri phosphate ratios were significantly decreased in TB animals (19.94 +/- 4.5, 81.51 +/- 12.8, and 4.20 +/- 0.8 mu moles/gm dry weight, respect ively) as compared with NTB animals (24.44 +/- 1.9, 116.72 +/- 75, and 4.81 +/- 0.4 mu moles/gm dry weight respectively, p < 0.05) and RES a nimals (24.08 +/- 3.3, 124.10 +/- 12.2, and 5.19 +/- 0.5 mu moles/gm d ry weight, respectively, p < 0.05). Conclusions. These alterations in high energy phosphate compounds in liver and skeletal muscle indicate that although the energy charge is maintained, energy depletion occurs early in the tumor-bearing state. These changes are tumor specific, n ot related to anorexia, and revert to non-tumor-bearing levels after t umor resection.