Inhibition of membrane transport of 5-fluoro[6-3H]deoxyuridine into L5178Y mouse leukemia cells.
The influx of 1.0 muM 5-fluoro[6-3H]deoxyuridine (5F[6-3H]dUrd) into L5178Y mouse leukemia cells followed a linear function with time from 2 to 10 min. Ammonium 5-bromodeoxyuridine 5'-methylphosphonate (BrdUrd-OPO2Me) inhibited the membrane transport of 5F[6-3H]dUrd into L5178Y cells. Influx of 5F[6-3H]dUrd into inhibited cells was observed from zero to 3 min; after 3 min the net rate of 5F[6-3H]dUrd uptake into the cells treated with 18 muM BrdUrd-OPO2Me was almost zero. The cellular uptake of 2'-deoxy[6-3H]uridine or 5-bromo[6-3H]deoxyuridine was inhibited by BrdUrd-OPO2Me. The L5178Y cells were grown for 96 hr in a medium that contained tritium-labeled BruDur-OPO2Me. An analysis of the labeled products in the growth medium showed that the ester linkage is not cleaved to separate the [3H]methylphosphonate group and the nucleoside moiety of BrdUrd-OPO2[3H]Me. The activity of thymidine kinase in a cell-free preparation from L5178Y cells was demonstrated. Although 37 muM 5-bromo-2'deoxyuridine produced an inhibition of approximately 45% in kinase activity, BrdUrd-OPO2Me had no effect on enzyme activity. The results indicate that BrdUrd-OPO2Me is an inhibitor of the cell membrane transport of the 5-fluoro and 5-bromo derivatives of 2'-deoxy[6-3H]uridine.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003857:Deoxyuridine / Q000378:metabolism; D005467:Floxuridine / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000201:enzymology / Q000378:metabolism*; D013937:Thymidine Kinase / Q000378:metabolism; D014316:Tritium
D005467:Floxuridine; D014316:Tritium; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D003857:Deoxyuridine