5-Fluorouracil, at lop4 M concentrations, inhibited ribosomal RNA maturation only slightly in Novikoff hepatoma cells growing in suspension culture. On a molar basis, 5-fluorouridine was a much more potent inhibitor of the maturation process. The difference between the effectiveness of 5-fluorouracil and 5-fluorouridine is probably a result of the greater transport and incorporation of the latt...

DNA topoisomerase I (Topo I) can exist in several different molecular weight forms in human leukemic cells. The Mr 98,000 form of Topo I was inhibited by several nucleoside triphosphates and their analogues at a 500 microM concentration in the order: dideoxy-GTP greater than 2-bromo-dATP greater than dideoxy-ATP greater than dideoxy-CTP greater than 2-fluoro-dATP greater than 2-chloro-dATP. The...

To understand the mechanism of cellular resistance to the nucleoside analogue cytarabine (1-beta-D-arabinofuranosylcytosine, AraC), two resistant derivatives of the human leukemic line CCRF-CEM were obtained by stepwise selection in different concentrations of AraC. CEM/4xAraC cells showed low AraC resistance, whereas CEM/20xAraC cells showed high resistance. Both cell lines showed similar patt...

Entecavir (ETV) is a potent nucleoside analogue against hepatitis B virus (HBV), and the emergence of drug resistance is rare in nucleoside-naive patients because development of ETV resistance (ETVr) requires at least three amino acid substitutions in HBV reverse transcriptase. We observed a case of genotypic ETVr with viral and biochemical breakthrough during ETV treatment of nucleoside-naive ...

Genetic defects in human purine nucleoside phosphorylase cause T-cell deficiency as the major phenotype. It has been proposed that efficient inhibitors of the enzyme might intervene in disorders of T-cell function. Compounds with features of the transition-state structure of purine nucleoside phosphorylase were synthesized and tested as inhibitors. The transition-state structure for purine nucl...

This July 2014 edition of the IAS–USA drug resistance mutations list updates the figures last published in March 2013.1 The following mutations have been added to existing classes or drugs: K65E/N has been added to the bars for the nucleoside and nucleotide analogue reverse transcriptase inhibitors (nRTIs) abacavir, didanosine, emtricitabine, lamivudine, stavudine, and tenofovir2; L100I has bee...