Document 0855
 DOCN  M9480855
 TI    Cellular mechanisms account for decreased anti-HIV-1 activity of
       nucleoside analogs.
 DT    9410
 AU    Doerr HW; Cinatl J Jr; Weber B; Cinatl J; Department of Medical
       Virology, J.W. Goethe University,; Frankfurt/M, Federal Republic of
       Germany.
 SO    Abstr Gen Meet Am Soc Microbiol. 1994;94:484 (abstract no. T-14). Unique
       Identifier : AIDSLINE ASM94/94313090
 AB    We tested whether cellular mechanisms (cell resistance) may account for
       decreased anti-HIV-1 activity of nucleoside analogs. For this aim
       several MOLT-4 cell sublines were established which exerted resistance
       against toxic effects of nucleoside analogs including AZT, ddI or ddC
       and MOLT-4 subline resistant to different cytotoxic agents (e.g.
       vincristine, daunomycin) so-called multidrug resistance. The results
       showed that anti-HIV-1 activities of AZT, ddI and ddC were significantly
       decreased in MOLT-4 sublines resistant to the respective nucleoside
       kinases. In the multidrug resistant MOLT-4 subline which expressed high
       levels of P-glycoprotein significantly decreased anti-HIV-1 activities
       of AZT and ddI were demonstrated. This effect was associated with
       decreased accumulation of the nucleoside analogs in the multidrug
       resistant cells. Our in vitro results showed that different cellular
       mechanisms (other than virus itself) may account for failure of
       nucleoside analogs to inhibit efficiently HIV replication.
 DE    Carrier Proteins/BIOSYNTHESIS  Cell Line  Didanosine/*TOXICITY  Drug
       Resistance  Human  HIV-1/*DRUG EFFECTS/PHYSIOLOGY  Membrane
       Glycoproteins/BIOSYNTHESIS  Tumor Cells, Cultured  Virus
       Replication/*DRUG EFFECTS  Zalcitabine/*TOXICITY  Zidovudine/*TOXICITY
       MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).