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Effects of Whole Blood or Albumin Fraction from Tumor-bearing Rats on Liver Protein Synthesis¹

Department of Biochemistry, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107

In a previous report from this laboratory, evidence was presented indicating that in perfusion experiments using normal livers (NL) and blood from Walker 256 tumor-bearing rats (WTB), there was significantly decreased incorporation of lysine into total serum protein than when blood from normal rats (NB) was used. A similar result was obtained when livers from tumor-bearing rats (WTL) were perfused with NB or WTB, less lysine being incorporated into total serum protein in WTB than in NB experiments. It was proposed that an inhibitory "signal factor(s)" (humoral) might be responsible for these results. This inhibitory signal factor activity was then traced to the broad albumin fraction of WTB in a series of experiments in which normal livers were perfused with normal blood to which was added the albumin fraction from the blood of normal or tumor-bearing rats.

The present study was undertaken to investigate the effects of the various perfusion media used in the above experiments on the synthesis of liver proteins by these same livers that were first studied with respect to serum protein synthesis. Incorporation of L-lysine-6-¹⁴C into liver protein was determined by: (a) precipitation of total liver protein with trichloroacetic acid; (b) oxidation of the washed and dried protein to ¹⁴CO₂ by the Schöniger method; (c) absorption of the ¹⁴CO₂ in an ethanolamine-ethylene glycol monomethyl ether solution; and (d) liquid scintillation counting. It was found that there was approximately twice as much incorporation in experiments in which either the liver or perfusing blood, or both, came from tumor-bearing rats (i.e., NL-WTB, WTL-NB, or WTL-WTB experiments), as compared to experiments in which liver and blood came from normal rats (NL-NB experiments).

It would appear from the results that, under the conditions of these experiments, whole WTB has a stimulatory effect on liver protein synthesis and an inhibitory effect on serum protein synthesis, whereas the broad albumin fraction of WTB has an inhibitory effect on both liver protein and serum protein synthesis. Some aspects of the results obtained appear to be related to priming effects on the perfused liver resulting from the growth of the extrahepatic tumor for approximately 2 weeks before removal of the liver from the rat.

¹ Supported in part by National Science Foundation Grant GB-23914 from the Physiological Processes Section and by Institutional General Research Support Grant RR05414.

Received 3/23/73. Accepted 7/ 9/73.