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Differences between 5-fluoro-2′-deoxyuridine and 5-fluorouridine in their cytotoxic effect on growth of murine lymphoma L5178Y cells in in vivo and in vitro systems

1980; Pergamon Press; Volume: 16; Issue: 8 Linguagem: Inglês

10.1016/0014-2964(80)90257-1

1879-2995

Fumihiko Kanzawa, Akio Hoshi, Kazuo Kuretani,

Synthesis and Biological Evaluation

The present studies were performed to determine the difference in vivo and in vitro conditions on the cytotoxic effects of FUdR and FUR by using the same cell line, L5178γ, in both systems. The prolonged activity of FUdR and FUR on survival time of tumor-bearing mice was examined. FUR increased the survival time to 58% over control at 3 mg/kg daily for 5 days; on the other hand, FUdR at 300 mg/kg (this being its optimal dose), did not show even the minimum effect. Namely, FUdR was less than one-hundredth of FUR in in vivo chemotherapeutic activity. The in vitro antiproliferating effects of FUdR and FUR varied under different experimental conditions as follows. In the cytotoxicity by continuous exposure to drugs on the proliferation of cells in culture, FUdR was approximately 8-fold higher than FUR. On the other hand, in the cytotoxicity by brief (60 min) exposure to drugs on the subsequent growth of cells cultured in a drug free medium, FUdR is about one-sixteenth of FUR. These observations indicate that the result of cytotoxicity by brief exposure but not continuous exposure, is reflected in vivo chemotherapeutic activity.