Higashigawa M, Ido M, Nagao Y, Kuwabara H, Hori H, Ohkubo T, Kawasaki H, Sakurai M
Department of Pediatrics, Mie University School of Medicine, Japan.
Leuk Res. 1991;15(8):675-81. doi: 10.1016/0145-2126(91)90069-6.
P388 murine leukemic cells 28.6-fold resistant to vincristine were cross-resistant to doxorubicin and etoposide. Although the intracellular ara-CTP in P388 murine leukemic cells resistant to vincristine (P388/VCR) was significantly higher than that in the parent cells, the cytotoxic effect of ara-C was not significantly different between the parent and resistant cells. Therefore, we investigated the DNA synthesis in P388/VCR and its parent cell line using the permeable cell system. The DNA synthesis in P388/VCR cells was less sensitive to ara-CTP and dTTP than that in P388 parent cells. These results suggested that the characteristics of DNA polymerase in P388/VCR cells might change when the cells developed multiple drug resistance.
对长春新碱具有28.6倍抗性的P388小鼠白血病细胞对阿霉素和依托泊苷也产生了交叉抗性。虽然对长春新碱耐药的P388小鼠白血病细胞（P388/VCR）内的阿糖胞苷三磷酸（ara-CTP）显著高于亲本细胞，但亲本细胞和耐药细胞之间阿糖胞苷（ara-C）的细胞毒性作用并无显著差异。因此，我们使用通透细胞系统研究了P388/VCR及其亲本细胞系中的DNA合成。P388/VCR细胞中的DNA合成对ara-CTP和脱氧胸苷三磷酸（dTTP）的敏感性低于P388亲本细胞。这些结果表明，当细胞产生多药耐药性时，P388/VCR细胞中DNA聚合酶的特性可能会发生变化。
