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Metabolic Adaptations in Rat Hepatomas: Altered Regulation of Serine Dehydratase Synthesis by Glucose and Amino Acids in Hepatocellular Carcinomas¹

McArdle Laboratory for Cancer Research, The University of Wisconsin Medical School, Madison, Wisconsin 53706

The forced feeding of amino acid mixtures to rats bearing the Morris 5123 hepatoma had virtually no effect on changing the already high levels of serine dehydratase present in this neoplasm. On the other hand a similar regimen did stimulate an increase in the level of serine dehydratase in the Morris 7800 and Reuber H-35 hepatomas. Glucose administration together with the amino acids had virtually no effect on changing or inhibiting the stimulated levels of the amino acids in the hepatomas. By quantitative precipitin techniques and pulse labeling with valine-¹⁴C, it was demonstrated that the rate of synthesis of serine dehydratase in the Morris hepatoma 5123 was extremely high relative to total soluble protein synthesis and that the administration of amino acids or glucose had no effect on valine incorporation into serine dehydratase. The results obtained apparently were not the result of a dramatically different structure of the serine dehydratase of the neoplasms, nor were they a result of the relative unavailability of glucose to the neoplasms because of their different blood supplies. The data presented indicate a deranged effect of glucose on enzyme synthesis, probably the result of altered mechanisms of the translational control of enzyme synthesis.

¹ The work reported herein was supported in part by National Cancer Institute Grant CA-07175 and American Cancer Society Grant P-314.

² Present address: Division of Research, National Jewish Hospital, Denver, Colo. 80206.

³ Career Development Awardee (CA-40415) of the National Cancer Institute.

Received 1/27/69. Accepted 6/10/69.