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• W2332896732 abstract "In leukemic cells exposed to 2-chlorodeoxyadenosine (2-CdA), levels of the nucleoside drug and its phosphate metabolites decay with time in the absence of external 2-CdA; an intrinsic part of this process is the efflux of 2-CdA. The effects of nitrobenzylthioinosine (NBMPR) and of dipyridamole (DPM), both potent inhibitors of es (e, equilibrative; s, sensitive to NBMPR) nucleoside transport processes, were studied in four lines of cultured leukemic lymphoblasts. Suspensions of 2-CdA-loaded cells were diluted 10-fold with 2-CdA-free medium to initiate the cellular 2-CdA decay processes, which followed a biexponential time course. When diluting media contained NBMPR or DPM, intracellular levels of 2-CdA and its metabolites were substantially increased (P < 0.001) compared with cells in media lacking the transport inhibitors, and 2-cda loss followed a monoexponential time course. As a consequence, the aucs (area under time-course plots of intracellular 2-cda and its metabolites) were significantly (P < 0.001) lower in untreated control cells compared to inhibitor-treated cells. These results suggest that nucleoside transport processes contribute to the efflux of 2-cda from the cultured lymphoblasts. The cytotoxicity of 1-h exposure to 2-cda of reh-a2 and ccrf-cem cells was enhanced three-fold by subsequent exposure to 0.5 μM NBMPR relative to that of control cells subjected to the same manipulations without NBMPR exposure. However, before such a strategy may be considered to have a therapeutic application, careful examination of effects in normal lymphocytes and ex vivo leukemic lymphoblasts must first be undertaken." @default.
• W2332896732 created "2016-06-24" @default.
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• W2332896732 date "2000-01-01" @default.
• W2332896732 modified "2023-10-15" @default.
• W2332896732 title "Enhancement of retention and cytotoxicity of 2-chlorodeoxyadenosine in cultured human leukemic lymphoblasts by nitrobenzylthioinosine, an inhibitor of equilibrative nucleoside transport" @default.
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• W2332896732 doi "https://doi.org/10.1038/sj.leu.2401633" @default.
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