Kim J H, Kim S H, Kolozsvary A, Khil M S
Henry Ford Hospital, Department of Radiation Oncology, Detroit, MI 48202.
Int J Radiat Oncol Biol Phys. 1992;22(3):515-8. doi: 10.1016/0360-3016(92)90865-f.
DNA topoisomerase I, a nuclear enzyme important for solving topologic problems arising during DNA replication, has been identified as a principal target of a plant alkaloid, 20(s)-camptothecin. In view of the profound biochemical effects of camptothecin and its analogues on DNA replication and the differential cytotoxic effects on human tumors in xenografts, experiments were performed to determine whether topotecan, a camptothecin analogue, would potentiate the radiation effects on human carcinoma cells in culture and murine fibrosarcoma in mice. Cell culture studies showed that a dose dependent reduction in cell survival was obtained with a 4 hr exposure of the drug following irradiation of cells. No enhancement of cell killing was seen when cells were treated with the drug before irradiation. Preliminary in vivo tumor studies showed a significant radiosensitizing effect of topotecan that was both drug dose (20 mg/kg) and time sequence (4 hr before irradiation) dependent. There was no enhanced skin reaction following the combined treatments.
DNA拓扑异构酶I是一种对解决DNA复制过程中出现的拓扑学问题至关重要的核酶，已被确定为一种植物生物碱20(s)-喜树碱的主要作用靶点。鉴于喜树碱及其类似物对DNA复制具有深远的生化影响，且对异种移植的人类肿瘤具有不同的细胞毒性作用，因此进行了实验，以确定喜树碱类似物拓扑替康是否会增强对培养的人类癌细胞和小鼠体内的鼠纤维肉瘤的辐射效应。细胞培养研究表明，在细胞照射后给予该药物4小时，细胞存活率呈剂量依赖性降低。在照射前用该药物处理细胞时，未观察到细胞杀伤增强。初步的体内肿瘤研究表明，拓扑替康具有显著的放射增敏作用，这与药物剂量（20mg/kg）和时间顺序（照射前4小时）有关。联合治疗后皮肤反应未增强。
