Nirdé P, Larroque C, Barnabé C
Unité mixte CNRS-ORSTOM UMR 9926, génétique moléculaire des parasites et des vecteurs, Montpellier, France.
C R Acad Sci III. 1995 Dec;318(12):1239-44.
In vitro benznidazole resistance was induced in cloned T. cruzi epimastigotes using a continuous drug pressure protocol. Stocks were selected according to their previous genetic characterization by multilocus enzyme electrophoresis. All the resistant clones were able to grow in long term cultivation in the presence of at least 50 microM benznidazole, which is the drug plasma level during chemotherapy in man. The highest level of resistance achieved was 220 microM. After differentiation of the epimastigote into the amastigote forms, the drug-resistance level was not affected. In both, the resistant epimastigotes and the resistant amastigotes, growth curves exhibited a lower growth rate than the sensitive counterparts without affecting the viability of the parasites. These data could be significant in basic research, to study the drug-resistance phenotype on relevant chemoresistant clones of T. cruzi, and to follow this phenotype after in vivo cycles.
使用连续药物压力方案在克隆的克氏锥虫前鞭毛体中诱导出体外苯硝唑抗性。根据之前通过多位点酶电泳进行的遗传特征分析选择虫株。所有抗性克隆在至少50微摩尔苯硝唑存在的情况下能够长期培养，这是人化疗期间的药物血浆水平。达到的最高抗性水平为220微摩尔。前鞭毛体分化为无鞭毛体形式后，耐药水平不受影响。在抗性前鞭毛体和抗性无鞭毛体中，生长曲线均显示出比敏感对应物更低的生长速率，而不影响寄生虫的活力。这些数据在基础研究中可能具有重要意义，可用于研究克氏锥虫相关化疗抗性克隆的耐药表型，并在体内循环后追踪该表型。
