Martens A C, de Groot C J, Hagenbeek A
Institute for Applied Radiobiology and Immunology/TNO, Rijswijk, The Netherlands.
Eur J Cancer. 1991;27(2):161-6. doi: 10.1016/0277-5379(91)90478-v.
A cyclophosphamide resistant subline (BNML/CPR) was developed in vivo in the BN rat acute myelocytic leukaemia (BNML) model. Full resistance was achieved after in vivo exposure of leukaemic animals to cyclophosphamide with, in total, 15 intraperitoneal injections of 100 mg/kg. The CPR line was cross-resistant to ifosfamide, but less so to mafosfamide. Continuous transplantation of the BNML/CPR line without a cyclophosphamide selection pressure resulted in the emergence of a subline (BNML/CPR greater than S) whose sensitivity to cyclophosphamide was similar to that of the parent BNML/S line. Both in the BNML parent line and in the BNML/CPR greater than S line, a 2p+ marker chromosome was present, whereas a 2p+q+ marker chromosome was characteristic for the BNML/CPR line. The mechanism of cyclophosphamide resistance can now be investigated in the BNML model at the DNA, at the mRNA and at the protein level.
在BN大鼠急性髓细胞白血病（BNML）模型中，通过体内培养建立了一种对环磷酰胺耐药的亚系（BNML/CPR）。白血病动物经体内环磷酰胺暴露，共15次腹腔注射100mg/kg后，获得了完全耐药性。CPR系对异环磷酰胺有交叉耐药性，但对马法兰的耐药性较弱。在没有环磷酰胺选择压力的情况下连续传代BNML/CPR系，出现了一个亚系（BNML/CPR＞S），其对环磷酰胺的敏感性与亲本BNML/S系相似。在BNML亲本系和BNML/CPR＞S系中，均存在一条2p+标记染色体，而BNML/CPR系的特征性标记染色体为2p+q+。现在可以在BNML模型中从DNA、mRNA和蛋白质水平研究环磷酰胺耐药的机制。
