Depletion of high energy phosphate compouds in the tumor-bearing state and reversal after tumor resection.
BACKGROUND
Cancer cachexia is a syndrome manifested by a variety of metabolic abnormalities that include depletion of host energy stores. We studied liver and skeletal muscle high energy phosphate compounds, inorganic phosphorus (Pi), and the energy charge in tumor-bearing (TB), pair fed non-tumor-bearing (NTB), and tumor-bearing resected (RES) rats.


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 animals were injected with 1 x 10(7)n methylcholanthrene (MCA)-induced sarcoma cells. On day 19, TB and NTB rat liver and skeletal muscle were analyzed 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, the level of liver adenosine monophosphate was significantly increased and the liver adenosine diphosphate level was decreased in the TB animals (3.55 +/- 0.6, 3.70 +/- 0.3 mumoles/gm dry weight, p < 0.05, p = 0.05, respectively) when compared with the NTB animals (3.06 +/- 0.4, 4.00 +/- 0.5 mumoles/gm dry weight, respectively). Muscle adenosine diphosphate levels were significantly decreased in the TB animals (1.57 +/- 0.7 mumoles/gm dry weight) as compared with NTB animals (2.23 +/- 0.7 mumoles/gm dry weight, p < 0.05). In addition, muscle adenosine triphosphate, phosphocreatine, and phosphocreatine/adenosine triphosphate ratios were significantly decreased in TB animals (19.94 +/- 4.5, 81.51 +/- 12.8, and 4.20 +/- 0.8 mumoles/gm dry weight, respectively) as compared with NTB animals (24.44 +/- 1.9, 116.72 +/- 7.5, and 4.81 +/- 0.4 mumoles/gm dry weight, respectively, p < 0.05) and RES animals (24.08 +/- 3.3, 124.10 +/- 12.2, and 5.19 +/- 0.5 mumoles/gm dry 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, not related to anorexia, and revert to non-tumor-bearing levels after tumor resection.
Hochwald
S N
SN
Surgical Metabolism Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Harrison
L E
LE
Port
J L
JL
Blumberg
D
D
Brennan
M F
MF
Burt
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002100:Cachexia / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000601:surgery; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D010710:Phosphates; D010725:Phosphocreatine; C025403:phosphocreatinine; D000255:Adenosine Triphosphate