ASSESSING THE INTERACTION OF IRRADIATION WITH ETOPOSIDE OR IDARUBICIN
ASSESSING THE INTERACTION OF IRRADIATION WITH ETOPOSIDE OR IDARUBICIN
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DOI：
10.4065/70.11.1053
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发表时间：
1995-11-01
影响因子：
8.9
通讯作者：
BONNER, JA
中科院分区：
文献类型：
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作者：
HADDOCK, MG;AMES, MM;BONNER, JA
目的：比较两种拓扑异构酶LI抑制剂依托泊苷和伊达阿比星与辐射的相互作用。设计：采用两种数学模拟系统来评估两者的相互作用。方法和结果：地鼠肺成纤维细胞(V79)在照射前或照射后立即给予依托泊苷或伊达阿比星24小时，照射后用依托泊苷或伊达阿比星处理可导致放射增敏，平均灭活剂量减少，照射前暴露于任何一种药物都不会导致放射增敏。首先使用的数学模拟系统是等效线分析，这种分析表明，如果照射后依托泊苷或伊达阿比星联合照射，两者的相互作用是在加性、辐射前的包络范围内的。照射和照射后的伊达比星暴露也导致了加性范围内的相互作用，而辐射前的伊达比星暴露导致的相互作用略低于相加作用，其次，根据中间效应原理进行分析。依托泊苷与照射、伊达比星与照射存在协同作用，照射后药物暴露(无论是伊达比星还是依托泊苷)协同作用更明显，不同照射剂量与药物浓度比的实验表明，协同作用的可能性随着药物浓度的增加而增加。结论：-照射与拓扑异构酶II活性物质的相互作用有待于在人肿瘤细胞系中进一步探讨。
Objective: To compare the interactions of two topoisomerase LI inhibitors, etoposide and idarubicin, with irradiation.Design: Two mathematical modeling systems were used to assess the interactions.Methods and Results: Hamster lung fibroblast cells (V79) were exposed to etoposide or idarubicin for 24 hours before or immediately after irradiation, Postradiation treatment with etoposide or idarubicin resulted in radiosensitization, as demonstrated by a decrease in the mean inactivation dose, Exposure to either drug before irradiation resulted in no radiosensitization, The first mathematical modeling system used was isobologram analysis, This analysis revealed a synergistic interaction if etoposide exposure followed irradiation, The interaction from the combination of irradiation and preradiation etoposide was within the envelope of additivity, Irradiation and postradiation idarubicin exposure also resulted in an interaction within the envelope of additivity, whereas preradiation idarubicin exposure resulted in a slightly less than additive interaction, Next, analyses were performed by the median effect principle. Synergistic interactions were demonstrated for combinations of etoposide and irradiation as well as idarubicin and irradiation, Synergistic interactions were more likely when drug exposure (either idarubicin or etoposide) followed irradiation, Experiments at various ratios of radiation dose to drug concentration showed that the likelihood of a synergistic interaction increased as the drug concentration increased relative to the radiation dose.Conclusion: The interaction of-irradiation with topoisomerase II-reactive agents should be further explored in human tumor cell lines.