Metabolic Adaptations in Rat Hepatomas II. Tryptophan Pyrrolase and Tyrosine -Ketoglutarate Transaminase*

The administration of t ryptophan or cortisone to rats bearing the Morris 5123 Hepatoma resulted in significant increases in t ryptophan pyrrolase activity in the host liver but in no change in the low tryptophan pyrrolase activity of the neoplasm. The repressed level of this enzyme in the neoplasm was not a result of the lack or excess of cofactors or enzymes necessary for the assay procedure employed, nor was it due to inhibitors present in the tissue. By means of induction with CIMabeled tryptophan, the acid-soIuble and protein fractions of both the l iverand tumor were found to contain essentially the same quantity of the labeled compound at the end of the induction period, showing tha t the failure of the response of t ryptophan pyrrolase of Hepatoma 5123 was not due to an inadequate amount of inducer available to the neoplasm. The tyrosine a-ketoglutarate transaminase activity of t tepa toma 5123 was very high (derepressed) in tumors carried in intact hosts. Tyrosine or cortisone administration did not change the level of the enzyme in the tumor significantly, although both agents increased the activity of the host liver markedly. The tyrosine a-ketoglutarate transaminase of Hepatoma 5123 in adrenalectomized hosts was much lower than tha t in tumors in intact animals. Administration of cortisone to adrenalectomized animals markedly stimulated the activity of this enzyme in the hepatoma. A simple working hypothesis is presented, based on these and related findings, to explain the biologic malignancy expressed by the Morris Hepatoma 5 1 ~ .