Putrescine administration reduces the rate of DNA synthesis in Ehrlich ascites tumor cells in vivo

Abstract

1. 1. Ehrlich ascites tumor cells exhibit a very low level of ornithine decarboxylase (ODC) activity during plateau phase growth. Upon transplantation of the tumor into a new recipient, however, the ODC activity increases precipitously. 2. 2. A 150-fold increase in ODC activity was evident at 4 hr after transplantation. This increase was almost completely eradicated following multiple injections of putrescine (25 μmols/mouse/hr). 3. 3. Putrescine treatment elicited the appearance of an intracellular protein inhibitor of ODC, an ODC-antizyme, which inhibited the ODC activity by complex formation with the enzyme. 4. 4. The enzyme-inhibitor complex was stable during low-salt Sephadex (G-75 Superfine) chromatography, but in the presence of 250 mM Nad the complex dissociated and both ODC and ODC-antizyme were recovered after separation on the Sephadex column. 5. 5. The administration of putrescine exerted an inhibitory effect on tumor cell proliferation; there was a lower rate of DNA synthesis and a decrease in the mitotic index.