Altered Amino Acid Kinetics in Rats with Progressive Tumor

The present study was designed to determine whether alter ations 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 Ill) 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 com pared 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 tumor bearing compared to pair-fed animals. The findings suggest that significant alterations in protein metabolism occur in ad vanced stages of experimental neoplastic disease which can not be explained by reductions in dietary intake and are aimed at providing adequate quantities of endogenous amino acids for net tumor growth.