RESUMEN
Resistance of Friend murine erythroleukemia cells was induced or selected by continuous stepwise exposure to adriamycin (ADM). The resistance index (R.I.) varied with different "mdr type" drugs, even when the compounds were closely related as ADM and daunorubicin (DNR). The cell uptake of anthracycline, evaluated by flow cytometry (FCM), was better correlated with the R.I. than the HPLC assessment. The quantitative cytology showed nuclear changes (size and color distribution); all the modifications were in part dependent on the degree of resistance. This study showed that the graded resistant sublines differed in their resistant phenotypes apart from their different degree of resistance.
Asunto(s)
Doxorrubicina/farmacología , Leucemia Eritroblástica Aguda/patología , Animales , Cromatografía Líquida de Alta Presión , Doxorrubicina/análisis , Doxorrubicina/farmacocinética , Resistencia a Medicamentos , Virus de la Leucemia Murina de Friend , Amplificación de Genes , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Ratones , Células Tumorales CultivadasRESUMEN
The retention of adriamycin in 5 Friend cell sublines of increasing degree of resistance was enhanced in vitro by three compounds: verapamil, nigericine and vanadate. Vanadate had the strongest activity, it enhanced also the incorporation in sensitive cells. Its efficacy was increased by a pre-incubation with H2O2. The effect of vanadate was then tested in vivo. When the tumor was transplanted i.p. and the treatment was also i.p., vanadate enhanced the efficacy of adriamycin, but it had also an antitumor activity by itself. Vanadate alone had some efficacy on the Friend cells of the lowest degree of resistance, when adriamycin had no effect. Nevertheless, vanadate had a partial cross resistance with adriamycin on these cells. When the tumor was transplanted subcutaneously and the treatment was still i.p., vanadate had no effect whilst adriamycin was still active.