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Effects of Polyamine Depletion on Proliferation and Differentiation of Murine Erythroleukemia Cells¹

Division of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

The polyamines putrescine, spermidine, and spermine have been implicated in the regulation of both cell proliferation and differentiation. We have monitored the relationship of intracellular polyamine levels with proliferation and differentiation of murine Friend erythroleukemia (MEL) cells. The omithine decarboxylase inhibitor, -difluoromethylornithine, has been used to inhibit MEL proliferation by depleting intracellular putrescine and spermidine. This inhibition of MEL proliferation is abrogated by exogenous putrescine, spermidine, or spermine. The measurement of intracellular polyamine levels following the addition of these exogenous polyamines demonstrates that spermidine is required for MEL proliferation. Further, we have found a highly significant relationship (p < 0.0001) between intracellular spermidine levels and MEL proliferation. The results also demonstrate that spermidine is required for induction of MEL differentiation by dimethyl sulfoxide, hexamethylene bisacetamide, and butyric acid. Moreover, there is a highly significant relationship (p < 0.0001) between MEL proliferation and differentiation. The present study thus suggests that spermidine is involved in cell proliferation and, thereby, differentiation of MEL cells.

¹ This investigation was supported by USPHS Grants CA 19589 and CA 29431, awarded by the National Cancer Institute, Department of Health and Human Services.

² Recipient of an American Cancer Society faculty research award. To whom requests for reprints should be addressed, at Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 9/12/83. Accepted 1/ 4/84.