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.