Increased cytotoxicity of N6-(delta 2-isopentenyl)adenosine in combination with pentostatin against L-1210 leukemia cells.

ABSTRACT

Pentostatin (I), a tight-binding inhibitor of adenosine deaminase, was evaluated in combination with the partially effective antitumor nucleoside N6-(delta 2-isopentenyl)adenosine (II) for cytotoxic activity against cultured L-1210 lymphocytic mouse leukemia cells. Although I alone (less than or equal to 10 micrograms/ml) was ineffective, it significantly potentiated and prolonged the cytotoxic and cytostatic activities of II. The combination of I (2-10 micrograms/ml) with II (25 micrograms/ml) resulted in inhibition of cellular proliferation (80-96%) within 24 hr with maintenance at that level for an extended period of time due to the continued ability of I to prevent the facile deamination of the allylic side chain of II. This type of adjuvant chemoprotection has potential use for other labile oncologic agents.