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Effect of -Difluoromethylornithine Alone and in Combination with Doxorubicin Hydrochloride, cis-Diamminedichloroplatinum(II), and Vinblastine Sulfate on the Growth of P3J Cells in Vitro

Medical Research [E. D. A.], Veterans Administration Medical Center [E. D. A.], Ann Arbor 48105, and Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan [R. B. N.], Ann Arbor, Michigan 48109

-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, was examined as a single and combined agent in growth studies using P3J, a Burkitt's lymphoma cell line. Used alone, DFMO (50 µg/ml; 0.21 mM) prevents cell proliferation in liquid culture and reduces the number and size of colonies that form in a two-layer soft agar system. In combination studies in which the soft agar system was used, DFMO was used at 15 and 25 µg/ml, concentrations which reduced the number of colonies to approximately 65 and 50%, respectively, of control plates. When doxorubicin hydrochloride (Adriamycin) was combined with DFMO, synergistic effects were noted at both DFMO concentrations. Cisplatin and DFMO were synergistic at the higher DFMO concentration and were supraadditive at 15 µg DFMO/ml. Combination studies using vinblastine sulfate (Velban) with DFMO did not deviate significantly from the predicted additive response.

¹ To whom requests for reprints should be addressed, at Veterans Administration Medical Center, 2215 Fuller Road, Ann Arbor, MI 48105.

Received 8/19/85. Revised 2/ 3/86. Revised 4/ 8/86. Accepted 4/ 9/86.