An analysis of vincristine-resistance in BHK cells pretreated with 1-beta-D-arabinofuranosylcytosine.
As with SV40-transformed BHK cells (1), pretreatment of BHK cells with 1-beta-D-arabinofuranosylcytosine (araC) very markedly enhanced the resistance frequency to N-phosphonoacetyl-L-aspartate (PALA) but only modestly increased the resistance frequency to vincristine (VCR). AraC pretreatment of cells that already had moderate VCR-resistance again only modestly enhanced the resistance frequency at a higher VCR concentration. By contrast, delaying the addition of VCR to BHK cells by 7-24 hours after pretreatment with araC increased the enhancement of VCR-resistance frequency to a level comparable to the enhancement of PALA-resistance frequency. VCR-resistant clones isolated without or after araC pretreatment were analysed for amplification of the multidrug resistance (mdr) gene. One of four clones isolated by single-step selection with no araC pretreatment and four of six clones isolated after araC pretreatment showed amplification of the mdr gene. All VCR-resistant clones tested were cross-resistant to actinomycin D and VCR-resistance was inhibited by treatment with verapamil.
Chen
Y
Y
Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill 27519.
Goz
B
B
Kirkman
L
L
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology*; D004347:Drug Interactions; D004351:Drug Resistance; D005784:Gene Amplification / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010641:Phenotype; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014750:Vincristine / Q000494:pharmacology*
D003561:Cytarabine; D001224:Aspartic Acid; D014750:Vincristine; C013195:sparfosic acid; D010746:Phosphonoacetic Acid