Abstract
It has recently been stated that MTX can cause DNA strand breaks. Ara-C, on the other hand, inhibits DNA repair synthesis after UV irradiation or exposure to chemical agents. Therefore, we investigated the accumulation of DNA strand breaks in a human promyelocytic leukemia cell line, HL-60, treated with methotrexate (MTX) and 1-β-D-arabinofuranosylcytosine (Ara-C). The sequential treatment with MTX (0.01-10μM) then Ara-C(10μM) had a synergistic effect on the formation of DNA strand breaks, which was dependent on MTX concentration. On the other hand, when Ara-C preceded MTX, no such synergism was observed. The addition of both Lhymidine(10μM) and hypoxanthine(100μM) to this system, but not thymidine or hypoxanthine alone, abolished the synergism. Pretreatmcnt with MTX augmented Lhe generation of 1-μ-D-arabinofuranosylcytosine 5′-triphosphate and the incorporation of Ara-C into DNA. However, these augmentation did not necessarily correlate with the amount of strand breaks. Whatever the underlying mechanism of this synergism is, our present data provide one possible biochemical basis for sequential MTX and Ara-C therapy.
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Tanizawa, A., Kubota, M., Takimoto, T. et al. 155 SEQUENTIAL COMBINATION OF METHOTREXATE AND l-β-D-ARABINOFURANOSYLCYTOSINE SHOWS SYNERGISTIC EFFECT ON THE GENERATION OF DNA STRAND BREAKS IN A HUMAN PROMYELOCYTIC LEUKEMIA CELL LINE. Pediatr Res 24, 137 (1988). https://doi.org/10.1203/00006450-198807000-00179
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DOI: https://doi.org/10.1203/00006450-198807000-00179