Apoptosis of muscle cells causes weight loss prior to impairment of DNA synthesis in tumor-bearing rabbits

Abstract

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.