Nishimura T, Suzuki H, Muto K, Tanaka N
J Antibiot (Tokyo). 1979 May;32(5):518-22. doi: 10.7164/antibiotics.32.518.
The biochemical mechanism of anthracycline resistance was studied with an adriamycin-resistant subline of mouse lymphoblastoma L5178Y cells. Both uridine and thymidine uptakes in the resistant cells were observed more resistant to adriamycin and daunorubicin than those in the parental cells. Aclacinomycin A exhibited the same degree of inhibition of nucleic acid syntheses in the sensitive cells and in the resistant cells. The resistance pattern observed by the inhibition of RNA and DNA syntheses seemed to parallel that by growth inhibition. No significant difference was demonstrated between the parental and resistant cells in the inhibition of RNA and DNA polymerase reactions with isolated nuclei. The uptake and retention of [3H]adriamycin was observed significantly less in the resistant cells than in the sensitive cells. The results suggested that the adriamycin resistance may be due to alteration of the cytoplasmic membrane and/or cytoplasm, resulting in decreased uptake and retention of the antibiotic in the resistant cells.
利用小鼠淋巴瘤L5178Y细胞的阿霉素耐药亚系研究了蒽环类药物耐药的生化机制。与亲代细胞相比，耐药细胞中尿苷和胸苷的摄取对阿霉素和柔红霉素更具抗性。阿克拉霉素A对敏感细胞和耐药细胞中核酸合成的抑制程度相同。通过抑制RNA和DNA合成观察到的耐药模式似乎与通过生长抑制观察到的模式平行。在分离细胞核的RNA和DNA聚合酶反应抑制方面，亲代细胞和耐药细胞之间未显示出显著差异。与敏感细胞相比，耐药细胞中[3H]阿霉素的摄取和保留明显较少。结果表明，阿霉素耐药可能是由于细胞质膜和/或细胞质的改变，导致耐药细胞中抗生素的摄取和保留减少。
