Cross-resistance to anti-HIV nucleoside analogs in multidrug-resistant human cells.
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.
Yusa
K
K
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Oh-hara
T
T
Yamazaki
A
A
Tsukahara
S
S
Satoh
W
W
Tsuruo
T
T
D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D016047:Zalcitabine / Q000378:metabolism* / Q000633:toxicity; D015215:Zidovudine / Q000378:metabolism* / Q000633:toxicity
D015215:Zidovudine; D016047:Zalcitabine