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Imbalance in Ornithine Metabolism in Hepatomas of Different Growth Rates as Expressed in Formation of Putrescine, Spermidine, and Spermine¹

The Ben May Laboratory for Cancer Research, University of Chicago, Chicago, Illinois 60637 [H. G. W.-A., G. L. C.], and Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana 46202 [G. W.]

In comparison with normal livers from rats of the same age, sex, and dietary regimen, the L-ornithine decarboxylase (EC 4.1.1.17) activities of fast-growing Morris hepatomas (e.g., lines 3924A and 7777) were very high, whereas a number of slow-growing and more differentiated hepatomas exhibited L-ornithine decarboxylase activities which were considerably less elevated.

None of the hepatomas examined, regardless of their speed of growth, had significantly elevated S-adenosylmethionine decarboxylase activities in comparison with that of liver.

The steady-state concentration of putrescine in some but not all of the fast-growing neoplasms was much greater than that in the corresponding normal liver controls. The putrescine content of all slow-growing hepatomas was usually above normal hepatic range.

The spermidine/spermine ratio tended to be higher in all of the hepatomas studied than in the corresponding normal livers; the overall concentrations of these two polyamines in all tumors were, however, within the range seen in the normal livers (0.6 to 1.5 µmoles/g.)

The utilization of L-ornithine for aliphatic polyamine synthesis versus the operation of the urea cycle in rat liver and its neoplasms is discussed.

¹ This is Paper 1 in a series of publications on "Metabolic Imbalance in L-Ornithine Utilization in Hepatomas of Different Growth Rates."

² Recipient of USPHS Grant HD-04592. To whom requests for reprints should be addressed, at the Ben May Laboratory for Cancer Research University of Chicago, Chicago, Ill. 60637.

³ Recipient of USPHS Grant CA-05034 and Grants from the American Cancer Society and Damon Runyon Memorial Fund, Inc.

Received 3/24/72. Accepted 6/ 1/72.