Effects of 2',3'-dideoxynucleosides on mammalian cells and viruses.

摘要: Previous studies on the biological effects of 2',3'-dideoxynucleosides (ddNs) have shown that while ddAdo is lethal to E. coli, ddThd has minimal growth mammalian cell lines and it inhibits retrovirus infection some but not others. also 5'-triphosphate ddThd, ddTTP, selectively cellular DNA polymerases beta gamma retroviral reverse transcriptases. Cellular polymerase alpha relatively resistant ddTTP. We extended these findings show 5'-triphosphates other 3 ddNs (ddATP, ddCTP, ddGTP) affect alpha, beta, in same fashion as does all four concentrations up 100 microM negligible NIH Swiss 3T3 cells. These may be due inefficient intracellular phosphorylation each nucleoside triphosphate. determined that, several different lines, phosphorylated only at a very slow rate one line tested (monkey CV-1 cells), ddGuo are poorly phosphorylated. Both ddGuo, probably converted by cells additional unknown compounds which activity. The display magnitudes certain virus infections. Although 30 herpes simplex I 50%, no effect. Infection 334C murine leukemia inhibited 70-80% ddAdo, ddCyd, 50 microM, inhibition 100%.