Cross-resistance to anti-HIV nucleoside analogs in multidrug-resistant human cells

Biochem Biophys Res Commun. 1990 Jun 29;169(3):986-90. doi: 10.1016/0006-291x(90)91991-z.

Abstract

Human multidrug-resistant K562/ADM cells showed 12-fold and 31-fold resistance to AZT (3'-azido-2', 3'dideoxythymidine) and DDC (2', 3'-dideoxycytidine), respectively. Other multidrug-resistant human cells CEM/VLB100 and AdrRMCF-7 also showed resistance to these nucleoside analogs. However, verapamil (10 microM) failed to reverse the resistance to the nucleoside analogs. Accumulation of [3H]AZT in human multidrug-resistant K562/ADM, CEM/VLB100 and AdrRMCF-7 cells decreased by 23, 35, and 42% respectively, as compared to their parental cells. These results suggest that anti-HIV nucleoside analogs including AZT, DDC could be transported by outward drug-transport system in the multidrug-resistant cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cell Division / drug effects
  • Cell Line
  • Drug Resistance*
  • Humans
  • In Vitro Techniques
  • Zalcitabine / metabolism*
  • Zalcitabine / toxicity
  • Zidovudine / metabolism*
  • Zidovudine / toxicity

Substances

  • Zidovudine
  • Zalcitabine