ISSN:
0021-9541
Keywords:
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Medicine
Notes:
Previous studies on the biological effects of the 2′,3′-dideoxynucleosides (ddNs) have shown that while ddAdo is lethal to E. coli, ddThd has minimal effects on the growth of mammalian cell lines and that it inhibits retrovirus infection of some cell lines but not others. Previous studies have also shown that the 5′-triphosphate of ddThd, ddTTP, selectively inhibits cellular DNA polymerases β and γ and retroviral reverse transcriptases. Cellular DNA polymerase α is relatively resistant to ddTTP. We have extended these findings to show that the 5′-triphosphates of the other 3 ddNs (ddATP, ddCTP, and ddGTP) affect cellular DNA polymerases α, β, and γ in the same fashion as does ddTTP. We also show that all four ddNs in concentrations up to 100 μM have negligible effects on the growth of NIH Swiss 3T3 cells. These negligible effects may be due to inefficient intracellular phosphorylation of each nucleoside to the triphosphate. We have determined that, in several different cell lines, ddThd is phosphorylated only at a very slow rate to ddTTP, and in the one cell line tested (monkey CV-1 cells), ddAdo and ddGuo are also poorly phosphorylated. Both ddAdo and ddGuo, and probably ddThd, are converted by CV-1 cells to additional unknown compounds which may have biological activity. The four ddNs display effects of different magnitudes on certain virus infections. Although 30 μM ddThd inhibits herpes simplex I infection of CV-1 cells by 50%, 30 μM ddAdo has no effect. Infection of NIH Swiss 3T3 cells by 334C murine leukemia virus is inhibited 70-80% by ddAdo, ddCyd, and ddThd at 50 μM, but inhibition by 50 μM ddGuo is 100%.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcp.1041210218
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