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 rats. Significant therapeutic effects were recorded after a treatment with 16 daily doses of PMEDAP at 5 mg/kg applied to the vicinity of the growing lymphoma. Identical administration of PMEA, or PMEG at a daily dose of 0.1 mg/kg did not affect the survival of lymphoma-bearing animals compared with untreated controls. A decrease in the lymphoma weight during PMEDAP administration was accompanied by the suppression of mitotic activity in neoplastic cells and increased chromatin condensation as witnessed by karyological examinations. Electron-microscopy showed the morphology of apoptotic cells (shrunken cells with condensed chromatin, apoptotic bodies) in lymphoma cell suspensions. An increase of nuclear DNA fragmentation was found during PMEDAP administration compared with spontaneous DNA fragmentation of untreated control lymphomas. These results indicate that PMEDAP application induces apoptosis in in vivo growing lymphomas. The antitumor effect of PMEDAP lasts only during the administration of the drug. After its cessation progression of neoplasia was reestablished.
Otová
B
B
Institute of Biology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. boto@lfl.cuni.cz
Francová
K
K
Franĕk
F
F
Koutník
P
P
Votruba
I
I
Holy
A
A
Sladká
M
M
Schramlová
J
J
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D016399:Lymphoma, T-Cell / Q000473:pathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C059499:9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine; D000225:Adenine