Schedule-dependent interaction of paclitaxel (Taxol) and irradiation in vitro.

L Plasswilm, N Cordes, R Sauer
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Abstract

The optimal dose and schedule of paclitaxel in combination with irradiation have not been determined yet. The aim of this study was to compare the in vitro cytotoxicity and enhancement of radiation sensitization as a function of single vs. fractionated paclitaxel exposure. A fibroblast cell line (B14) in exponential growth phase was used. The clonogenic assay was applied to determine cell survival. Flow cytometric measurements were performed to study cell cycle DNA distribution. Cytotoxicity of Taxol was examined at concentrations varying from 2 to 50 microM. Single (1 x 0 microM) vs. fractionated (2 microM/day, days 1-5) exposure of Taxol was investigated. The combination of Taxol plus irradiation as single and fractionated treatment was accomplished with 10 microM Taxol on day 1 plus 10 Gy irradiation on day 1 vs. Taxol 2 microM/day, days 1-5, plus irradiation 2 Gy/day, days 1-5. One-, 9-, and 24-hr intervals between end of incubation and irradiation were defined. Control populations demonstrated an average plating efficiency of 93%. Single Taxol exposure showed an average clonogenic survival of 84%. No significant difference between concentrations varying from 2 to 50 microM was observed. Single dose irradiation (1 x 10 Gy) led to clonogenic survival of 3%. Single exposure of Taxol plus single dose irradiation led to clonogenic survival of 4%. Fractionated radiation showed an average clonogenic survival of 41%. Fractionated Taxol treatment led to an average clonogenic survival of 63%. The combination of fractionated Taxol treatment (2 microM/day, days 1-5) plus fractionated irradiation (2 Gy/day, days 1-5) showed an average clonogenic survival of 15%. No significant difference between the chosen intervals was demonstrated. Flow cytometric measurements did not indicate any significant alterations in cell cycle DNA distribution. In conclusion, the data demonstrate a potential beneficial effect by combining fractionated Taxol exposure with fractionated irradiation without evidence for G2/M arrest in DNA analysis.

紫杉醇(Taxol)与体外辐照的时间依赖性相互作用。
紫杉醇联合照射的最佳剂量和方案尚未确定。本研究的目的是比较体外细胞毒性和辐射增敏的增强作为单一和分级紫杉醇暴露的功能。采用指数生长期成纤维细胞系(B14)。克隆生成法测定细胞存活率。流式细胞术检测细胞周期DNA分布。紫杉醇的细胞毒性在浓度2 ~ 50 μ m范围内进行了研究。研究了紫杉醇单次暴露(1 × 0 μ m)与分级暴露(2 μ m /天,1-5天)。紫杉醇加照射作为单次和分次治疗的组合,第1天10微米紫杉醇加第1天10 Gy照射vs.紫杉醇2微米/天,第1-5天,加照射2 Gy/天,第1-5天。定义孵育结束和照射之间1小时、9小时和24小时的间隔。对照群体的平均电镀效率为93%。单次紫杉醇暴露显示平均克隆存活率为84%。在2至50微米的浓度范围内,没有观察到显著差异。单次照射(1 x 10 Gy)导致克隆成活率为3%。紫杉醇单次照射加单次剂量照射导致克隆成活率为4%。分步放射显示克隆成活率平均为41%。分馏紫杉醇治疗导致平均克隆成活率为63%。分步紫杉醇处理(2微米/天,第1-5天)加分步照射(2 Gy/天,第1-5天)的组合显示,平均克隆存活率为15%。所选时间间隔之间无显著差异。流式细胞术测量未显示细胞周期DNA分布有任何显著改变。总之,数据表明,将紫杉醇分级暴露与分级辐照相结合,在DNA分析中没有出现G2/M阻滞的证据,具有潜在的有益效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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