Comparison of the DNA incorporation in human MOLT-4 cells of two 2'-beta-fluoronucleosides, 2'-beta-fluoro-2',3'-dideoxyadenosine and fialuridine.
Incorporation of 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA), a recently developed anti-HIV agent, into the cellular DNA of human MOLT-4 cells has been compared with the DNA incorporation seen with fialuridine (FIAU; 1-[2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl]-5-iodouracil), a potent anti-hepatitis B (anti-HBV) nucleoside analogue recently found to cause severe hepatic toxicity in human subjects. At equimolar concentrations (10 microM), incorporation of F-ddA was less than 1% of that for FIAU, a difference attributable to the lack of a 3'-hydroxyl group in the former compound and a consequent inability of F-ddA, unlike FIAU, to form DNA internucleotide linkages.
Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
G S
GS
Ahluwalia
J S
JS
Driscoll
H
H
Ford
D G
DG
Johns
D000998:Antiviral Agents / Q000378:metabolism*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans
D000998:Antiviral Agents; C055502:2-fluoro-2',3'-dideoxyadenosine; D001086:Arabinofuranosyluracil; D016048:Dideoxyadenosine; C043457:fialuridine; D004247:DNA