Alterations in ornithine decarboxylase (ODC) activity and in the polyamine and nucleic acid (RNA and DNA) concentrations were studied in P388 leukemia cells and in the host liver at different times after intraperitoneal inoculation of 5 × 10⁶ tumor cells into BDF₁ mice. ODC activity of leukemia cells had a maximum at day 5 after tumor transplantation. Cellular spermidine concentration declined significantly during the first 5 to 6 days. The RNA concentration of tumor cells changed parallel to that of spermidine. In the livers of ascites tumor-bearing mice ODC activity was 5- to 20-fold of control and had a maximum at days 5 to 6 after tumor cell inoculation. Spermidine concentration in the host liver increased, whereas spermine decreased gradually with tumor growth.

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In vivo effects of DL-α-difluoromethylornithine (DFMO) on the metabolism of polyamines and nucleotide phosphates were monitored in P388/S leukemia cells grown intra-peritoneally in BDF₁ inbred male mice. Inhibiting the ornithine decarboxylase (ODC) activity DFMO depleted putrescine and spermidine to 30–50 and 50–60%, respectively, and increased spermine to 25–60% compared with the controls, when given as 2% solution in drinking water of the tumor-bearing animals. DFMO treatment caused a parallel 56% elevation of total nucleotide content in tumor cells with distinct and significant increase of some nucleotide phosphates. The most pronounced alterations were shown in the intracellular UTP (202%), CTP (103%), ADP (92%) and ATP (71%) concentrations. Changes in polyamine and nucleotide phosphate metabolisms were dependent on tumor progression. A possible explanation of the metabolic events induced by DFMO is discussed.

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