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• W2108998082 abstract "Fluoro-5- methyl -1 -/A®-D-arabinofuranosyluracil(FMAU), like 2'-fluoro-5-iodo-1-/8-D-arabinofuranosylcytosine (FIAC), has potent antiviral activity, but unlike FIAC, It also has antileu- kemic effects. The two agents and 1-yS-o-arabinofuranosylcy- tosine (ara-C) are compared herein. Concentrations inhibiting thymidine (dThd) incorporation into DMA by 50% are for FMAU, FIAC, and ara-C, respectively, in L1210/0, 32, 353, and 0.2 fiM and in L1210/ara-C, 17, >10,000, and 3,900 JUM.Other FMAU analogs, 2'-fluoro-5-iodo-1-/S-D-arabinofuranosyluracil and 2'-fluoro-5-ethyl-1-yS-D-arabinofuranosyluracil, inhibit dThd incorporation equally in ara-C-sensitive and -resistant cells; however, their potencies are weaker than that of FMAU. Similar results are obtained when (3H)deoxyadenosine is used as a precursor of incorporation. In l_1210/0 cells, incorporation of (2-14C)FMAU radioactivity into DMA is competitively inhibited by dThd and deoxycytidine (dCyd), whereas the incorporation of (2-14C)FIAC radioactivity is competitively inhibited by dCyd but not appreciably by dThd. In L1210/ara-C cells, incorpo ration of (2-14C)FMAU is competitively inhibited by dThd but not by dCyd. In L1210/0 cells, FMAU has little inhibitory effect on the tritium release from (5-3H)deoxyuridine but markedly inhibits the incorporation of (2-14C)deoxyuridine into DMA. FIAC, by contrast, predominately inhibits the release of tritium from (5-3H)deoxyuridine but has little effect on subsequent incorporation into DNA. These results suggest that (a) FIAC, but not FMAU, is cross-resistant to ara-C; (b) FMAU is partic ularly effective against L1210/ara-C cells; (c) FIAC behaves metabolically like dCyd, and FMAU like dThd and dCyd; (d) dCyd and dThd may be used as chemotherapeutic modulators; and (e) FIAC predominately inhibits dThd kinase and/or thy midine monophosphate synthetase, whereas FMAU predomi nately inhibits DNA polymerase and/or nucleotide kinases. Similar conclusions were obtained when P815/0 and P815/ ara-C cells were used. The relative potencies of FIAC and FMAU in inhibiting dThd incorporation into DNA in leukemic sublines correlate with cytotoxicity in vitro and chemothera peutic effects in vivo." @default.
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• W2108998082 date "1982-10-01" @default.
• W2108998082 modified "2023-09-23" @default.
• W2108998082 title "Biochemical effects of 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil and 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine in mouse leukemic cells sensitive and resistant to 1-beta-D-arabinofuranosylcytosine." @default.
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