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Department of Medicine, University College London School of Medicine, The Rayne Institute, University Street, London WC1E 6JJ [P. W. E., M. J. R.], and Unit of Human Cancer Biology, Ludwig Institute for Cancer Research (London Branch), Royal Marsden Hospital, Sutton, Surrey, SM2 5PX [L. L.], England
Protein synthesis has been measured in vivo in liver and muscle of mice bearing the XK1 tumor, an appropriate model for cancer cachexia. Two different methods were used involving measurement of tracer incorporation into tissue protein either at the end of a 4-hr 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 hr). 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. It is concluded that the wasting which is associated with advanced malignant disease is brought about by a reduction in the rate of protein synthesis in the tissues, and that this cannot be explained by depression of food intake alone.
1 This work was supported by grants from the Cancer Research Campaign and the Wellcome Trust.
2 Present address: Department of Nutrition, Queen Elizabeth College, Campden Hill Road, London W8 7AH, England. To whom requests for reprints should be addressed.
3 Present address: Department of Physiology, University of Dundee, Dundee DD1 4HN, Scotland.
Received 7/13/83. Accepted 3/30/84.
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