Abstract
The sequence-dependency of the antitumor effect of etoposide (VP-16) and 1-B-D-arabinof uranosy lcytosine (ara-C) and its mechanism was investigated in L1210 bearing BDF1 mouse. Treatment with VP-16 of 15mg/kg and ara-C of 25mg/kg was administered intraperitoneally on days 1, 4, 7 after tumor inoculation. Seven of 10 mice treated with three hour-pretreatment with VP-16 followed by ara-C were Cured, but none of the mice treated with simultaneous administration was cured. Only 2 of 10 mice treated with the reverse sequence were cured.
To discuss the mechanism of this sequence-dependency, incorporation of ara-C into DNA was determined in combination with VP-16. On day 3 after tumor inoculation, VP-16 and 1μCi of (3H)ara-C was injected intraperitoneally. Three hour pretreatment with VP-16 increased incorporation of ara-C up to 230% of ara-C injection alone, while simultaneous administration of VP-16 decreased it by 67%.
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Ohkubo, T., Higashikawa, M., Kawasaki, H. et al. 102 SYNERGISTIC INTERACTION BETWEEN ETOPOSIDE AND 1-β-D-ARABINOFURANOSYLCYTOSINE. Pediatr Res 24, 128 (1988). https://doi.org/10.1203/00006450-198807000-00126
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DOI: https://doi.org/10.1203/00006450-198807000-00126