This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tayek, J. A. Articles by Brasel, J. A. Search for Related Content PubMed PubMed Citation Articles by Tayek, J. A. Articles by Brasel, J. A.

Effects of Tumor Necrosis Factor on Skeletal Muscle and Walker 256 Carcinosarcoma Protein Metabolism Studied in Vivo¹

Departments of Medicine [J. A. T., J. A. B.] and Pediatrics, [J. A. B.], University of California, Los Angeles, School of Medicine, Harbor-UCLA Medical Center, Torrance, California 90509

Human tumor necrosis factor (TNF) inhibits tumor growth, but its effects on tumor and skeletal muscle protein metabolism in vivo have not been adequately studied. Walker 256 carcinosarcoma growth rate was followed over an 11-day period in Sprague-Dawley rats. Tumor-bearing rats received either saline or 50 µg of TNF (Genentech, Inc.) s.c. on day 8 of tumor growth. This single dose of TNF reduced tumor protein growth during a 2-day posttreatment period from 27.6 ± 4.4 to 10.5 ± 3.7%/day (mean ± SE; P < 0.01). The rate of in vivo incorporation of L-[1-¹⁴C]leucine into skeletal muscle protein was significantly increased (P < 0.05) from 5.1 ± 0.2%/day in the saline-treated tumor-bearing rats to 7.7 ± 1.3%/day in the TNF-treated tumor-bearing rats. The latter value was not statistically different from the 9.2 ± 0.9%/day observed in the tumor-free control animals. TNF administration significantly increased both the total and individual acid-soluble skeletal muscle amino acid concentrations in tumor-bearing rats by an average of 86 ± 7%, compared to values in saline-treated tumor-bearing rats. Similarly, acid-soluble skeletal muscle 3-methyl-histidine concentrations increased from 66 ± 14 to 113 ± 19 pmol/g protein (P < 0.05). Tumor protein synthesis in the TNF-treated group was 50% greater than in the saline-treated group, whether expressed as %/day (72.7 ± 9.1 versus 47.9 ± 4.8; P < 0.05) or was µg/g tumor/min (58.7 ± 7.7 versus 40.7 ± 4.5; P < 0.05). In contrast, estimated tumor protein degradation rates were increased by over 200% in the TNF-treated rats, compared to the values in the saline-treated rats [62.1 ± 10.7 versus 20.3 ± 6.0%/day (P < 0.01) and 50.0 ± 8.9 versus 17.5 ± 5.4 µg/g tumor/min (P < 0.01)]. Thus, TNF appears to stimulate tumor protein degradation more than protein synthesis, explaining the overall decrease in tumor growth.

¹ Supported in part by NIH Grant T32-DK07461, Clinical Nutrition Research Unit Young Investigator Award 5P01-CA42710, and Harbor-UCLA Medical Center, Research and Education Institute, Investigator Research Award.

² To whom requests for reprints should be addressed, Division of Endocrinology and Metabolism, Martin Research Building, Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502.

Received 6/ 6/89. Accepted 1/23/90.