Effect of the dialdehyde derivative of 5'-deoxyinosine on pyrimidine deoxyribonucleoside metabolism in L1210 cells.
The effects of the dialdehyde derivatives of inosine (Inox) and 5'-deoxyinosine (5'-dInox) on L1210 cells were compared. The growth of L1210 cells was inhibited to a greater extent by 5'-dInox than by Inox. The increased inhibition of L1210 cell growth by 5'-dInox was also reflected by the increased inhibition of the incorporation of precursors into RNA, DNA and proteins. Even though 5'-dInox was a more potent inhibitor, Inox accumulated in the L1210 cells to levels 4- to 5-fold greater than 5'-dInox. The metabolism of [5-3H]deoxycytidine and [5-3H]deoxyuridine by L1210 cells in culture, in the presence of Inox or 5'-dInox, indicated that dCMP deaminase was an intracellular site of action for 5'-dInox. The dCMP deaminase activity in cell-free extracts prepared from 5'-dInox-treated cells was reduced markedly. This decrease in activity was not reversed by increased substrate concentrations nor was the activity subject to allosteric activation by dCTP. Deoxyuridine and deoxycytidine were able to reverse the effects of 5'-dInox on the inhibition of L1210 cell growth.
D000818:Animals; D002478:Cells, Cultured; D003844:DCMP Deaminase / Q000032:analysis; D003841:Deoxycytidine / Q000378:metabolism* / Q000494:pharmacology; D003857:Deoxyuridine / Q000378:metabolism* / Q000494:pharmacology; D007288:Inosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D013940:Thymidylate Synthase / Q000032:analysis
D003841:Deoxycytidine; C007390:inosine dialdehyde; D007288:Inosine; C020277:5'-deoxyinosine dialdehyde; D013940:Thymidylate Synthase; D003844:DCMP Deaminase; D003857:Deoxyuridine