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Antileukemic activity against L1210 leukemia, pharmacokinetics and hematological side effects of
Abstract:
The chemotherapeutic potential of 5-hydroxymethyl-2'-deoxyuridine (5HmdUrd) was examined in vitro and in vivo. The compound was toxic in 2-day cultures; 7, 66 and 88% inhibition in the growth of L1210 cells was achieved with 1, 10 and 100 microM 5HmdUrd, respectively. The maximal plasma concentration of 5HmdUrd at 15 min after a single i.p. injection (100 mg/kg) in DBA/2 mice was 193-244 mumol./l and the compound had a logarithmic disappearance curve with a half-life of 20 min. Chemotherapy given as two daily i.p. injections of 5HmdUrd (100 mg/kg) for five successive days resulted in a 239% increase in median lifespan and 2/6 long-term survivals among DBA/2 mice bearing leukemia L1210. This treatment resulted in temporary neutropenia and thrombocytopenia, which were followed by rebound thrombocytosis and neutrophilia of short duration. Our data indicate that 5HmdUrd can successfully be used in experimental cancer chemotherapy in vivo.