PROTEIN-SYNTHESIS MEASURED INVIVO IN MUSCLE AND LIVER OF CACHECTIC TUMOR-BEARING MICE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (7) , 2779-2784
Abstract
Protein synthesis was measured in vivo in liver and muscle of mice bearing the [human hypernephroma] XK1 tumor, an appropriate model for cancer cachexia. Two methods were used involving measurement of tracer incorporation into tissue protein either at the end of a 4 h constant infusion of [14C]tyrosine or 10 min after i.v. injection of a flooding dose of [3H]phenylalanine. Whole-body tyrosine flux was decreased by 60% in cachectic tumor-bearing mice, and protein synthesis was depressed by 70% in muscle and by 40% in liver. The depression of protein synthesis in muscle was due to a reduction in both RNA content (i.e., protein-synthesizing capacity) and RNA activity (i.e., protein synthesized per g of RNA per h). In liver, the depression of protein synthesis was due entirely to a decrease in RNA activity. The results also suggest that the synthesis of export proteins was affected more than the synthesis of fixed liver protein. Restriction of food intake in normal mice by up to 50% caused a loss of body weight and reductions in protein synthesis in liver and muscle which were less severe than those caused by the presence of the tumor. The wasting which is associated with advanced malignant disease is brought about by a reduction in the rate of protein synthesis in the tissues; this cannot be explained by depression of food intake alone.