Apoptosis of muscle cells causes weight loss prior to impairment of DNA synthesis in tumor-bearing rabbits.
The mechanism of weight loss induced by the growth of malignant tumors is still unknown. We investigated it by focusing on apoptosis of skeletal muscle. VX2-tumor was implanted into rabbits and the apoptotic index (AI) of skeletal muscle was measured by in situ end-labeling assay. Plasma of the tumor-bearing rabbits was perfused repeatedly through non-coated charcoal resin. The AI reached 54.6% early after tumor implantation, when weight loss amounted to an 18% decrease in lean body mass (LBM) without change in muscle DNA synthesis or urinary 3-methylhistidine / creatinine ratio (3-MH / Cr). When the decrease of LBM reached 30%, DNA synthesis was decreased by 48% and 3-MH / Cr was increased by 104%, whereas AI was only 4.7%. The plasma perfusion did not prevent apoptosis in muscle, but improved LBM, DNA synthesis, and 3-MH / Cr. There may be two mechanisms of muscle depletion during the tumor growth: apoptosis in the early stage and metabolic abnormalities in muscle in the late stage.
Ishiko
O
O
Department of Obstetrics and Gynecology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan. ishikoo@msic.med.osaka-cu.ac.jp
Sumi
T
T
Hirai
K
K
Honda
K I
KI
Nakata
S
S
Yoshida
H
H
Ogita
S
S
D000818:Animals; D017209:Apoptosis; D015992:Body Mass Index; D003404:Creatinine / Q000652:urine; D004247:DNA / Q000096:biosynthesis*; D053938:DNA Fragmentation; D020287:In Situ Nick-End Labeling; D008297:Male; D008762:Methylhistidines / Q000652:urine; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D011817:Rabbits; D015431:Weight Loss / Q000235:genetics / Q000502:physiology*
D008762:Methylhistidines; D004247:DNA; D003404:Creatinine; C028118:3-methylhistidine