Abstract
Guanine arabinoside (araG) and cytosine arabinoside (araC) are nucleoside analogs which elicit cytotoxicity through their corresponding 5′-triphosphate, metabolites. Although less potent than araC, araG is of interest as an antileukemic agent due to its selective toxicity to cultured T compared to B lymphoblasts. In order to determine whether araG would exhibit a similar selectivity of action in vivo, we have examined the metabolism of this drug in mononuclear cells from patients with leukemia. Peripheral blood was diluted and incubated with 100 μM araG or 10 μM araC for 4 hours. The highest level of araGTP accumulation occurred in leukocytes from patients with T-cell ALL (median value 187 pmol/107 cells). Cells from patients with AML or non-T-, non-B cell. ALL accumulated lower levels of araGTP (72 and 86 pmol/107 cells, respectively), and cells from patients with CLL accumulated the lowest amount of araGTP (31 pmol/107 cells). In contrast, accumulation of araCTP was similar in cells from patients with T-cell ALL, AML and non-T, non-B-cell ALL. The amount of araG or araC remaining in plasma after 4 hours varied and was not related to the cellular accumulation of the corresponding nucleotides. These results suggest that araG may act as a selective chemotherapeutic agent in patients with T-cell ALL.
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Shewach, D., Mitchell, B. 90 METABOLISM OF GUANINE ARABINOSIDE AND CYTOSINE ARABINOSIDE IN CELLS FROM PATIENTS WITH LEUKEMIA. Pediatr Res 24, 126 (1988). https://doi.org/10.1203/00006450-198807000-00114
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DOI: https://doi.org/10.1203/00006450-198807000-00114