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Nutrition/Metabolism Laboratory, Cancer Research Institute, New England Deaconess Hospital/Harvard Medical School, Boston, Massachusetts 02215
The present study was designed to determine whether alterations in host metabolism associated with progressive tumor growth were a result of the anorexia frequently observed with cancer or could be attributed to other direct tumor effects. Rates of tyrosine flux, oxidation, and incorporation into protein, as well as fractional protein-synthetic rates in nonsecretory liver, muscle, and tumor, were determined in overnight-fasted rats, 5 to 6 (Stage I), 10 to 11 (Stage II), and 15 to 16 (Stage III) days following s.c. implantation of RNC-254 fibrosarcoma. Tumor-bearing rats were allowed to consume a purified diet containing 20% protein ad libitum, and results were compared to non-tumor-bearing rats pair fed quantities of food equivalent to tumor-bearing animals or allowed to consume the diet ad libitum.
Results demonstrate that during later stages of tumor growth (Stage III) calorie intake and nontumor body weight gain were reduced in tumor-bearing rats (p < 0.05). Fifteen and 16 days following implantation, there were significant changes in amino acid kinetics that were not observed after earlier periods of tumor growth and that could not be explained by any reduction in dietary intake. Rates of tyrosine appearance in the plasma and subsequent incorporation into whole-body protein were increased 33 and 34%, respectively (p < 0.05), when compared to non-tumor-bearing rats fed equivalent quantities of food. Whole-body tyrosine oxidation rates were unchanged. Skeletal protein synthesis, as reflected by gastrocnemius or rectus abdominus muscle, was reduced from 10.5 and 10.1%/day to 7.4 and 6.0%/day, respectively (p < 0.05), in tumorbearing compared to pair-fed animals. The findings suggest that significant alterations in protein metabolism occur in advanced stages of experimental neoplastic disease which cannot be explained by reductions in dietary intake and are aimed at providing adequate quantities of endogenous amino acids for net tumor growth.
1 Supported in part by Grants GM-22691, GM-24401, and GM-24206, awarded by the National Institute of General Medical Sciences, and RR-05591, awarded by the Research Resources Division of the NIH, Department of Health, Education, and Welfare. This is Article 702 of the Cancer Research Institute, New England Deaconess Hospital.
2 To whom requests for reprints should be addressed, at Cancer Research Institute, 194 Pilgrim Road, Boston, Mass. 02215.
Received 7/13/81. Accepted 11/30/81.
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