9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP) - a potential drug against hematological malignancies - induces apoptosis

Antitumor activity of the acyclic nucleotide analogs PMEDAP, PMEA, and PMEG was studied on a model of a spontaneous T-cell lymphoma in inbred SD/cub m ts. Significant therapeutic effects were recorded after. a treatment with 1 6 daily doses of PMEDAP at 5 mg/kg applied to the vicinity of the growing l ymphoma. Identical administration of PMEA, or PMEG at a daily dose of 0.1 m g/kg did not affect the survival of lymphoma-bearing animals compared with untreated controls. A decrease in the lymphoma weight during PMEDAP adminis tration was accompanied by the supression of mitotic activity in neoplastic cells and increased chromatin condensation as witnessed by karyological ex aminations. Electron-microscopy showed the morphology of apoptotic cells (s hrunken cells with condensed chromatin, apoptotic bodies) in lymphoma cell suspensions. An increase of nuclear DNA fragmentation was found during PMED AP administration compared with spontaneous DNA fragmentation of untreated control lymphomas. These results indicate that PMEDAP application induces a poptosis in in vivo growing lymphomas. The antitumor effect of PMEDAP lasts only during the administration of the drug. After its cessation progressio n of neoplasia was reestablished.