NICOTINAMIDE, FLUOSOL DA AND CARBOGEN - A STRATEGY TO REOXYGENATE ACUTELY AND CHRONICALLY HYPOXIC CELLS INVIVO
NICOTINAMIDE, FLUOSOL DA AND CARBOGEN - A STRATEGY TO REOXYGENATE ACUTELY AND CHRONICALLY HYPOXIC CELLS INVIVO
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DOI：
10.1038/bjc.1991.22
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发表时间：
1991-01-01
影响因子：
8.8
通讯作者：
AOKI, DS
中科院分区：
文献类型：
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作者：
CHAPLIN, DJ;HORSMAN, MR;AOKI, DS
已经评价了烟酰胺和/或Fluosol DA和Carbogen呼吸治疗对500-750 mg SCCVII和KHT肿瘤辐射反应的影响。 用Fluosol DA/Carbogen或烟酰胺预处理导致相对适度的辐射损伤增强，使用体内/体外克隆形成终点观察到增强因子为1.1和1.3。 烟酰胺和Fluosol DA/Carbogen的组合在研究的辐射剂量范围内产生了更大的增强因子1.6。 这些修改因子反映的值接近该生存范围内完全有氧反应的预期值。 在SCCVII肿瘤中的生长延迟研究提供了类似的结果。 使用最近开发的荧光激活细胞分选技术，该技术利用双苯甲酰胺染料Hoechst 33342的体内药代动力学和DNA结合特性，评估烟酰胺和/或Fluosol DA/Carbogen方案对急性缺氧发生的影响。 结果清楚地表明，烟酰胺显著降低了“急性缺氧”的量，但对“慢性”缺氧细胞的影响较小。 然而，烟酰胺和Fluosol DA/Carbogen的组合显著增加了“急性”和“慢性缺氧”细胞的反应。 结果提供证据表明，烟酰胺和Fluosol DA/Carbogen的组合可以提供使急性和慢性缺氧细胞再氧合的有效方式。
The effect of Nicotinamide and/or treatment with Fluosol DA and Carbogen breathing on the radiation response of 500-750 mg SCCVII and KHT tumours has been evaluated. Pretreatment with Fluosol DA/Carbogen or Nicotinamide resulted in relatively modest enhancements of radiation damage with enhancement factors of 1.1 and 1.3 being observed using an in vivo/in vitro clonogenic end-point. A combination of Nicotinamide and Fluosol DA/Carbogen resulted in a larger enhancement factor of 1.6 over the radiation dose ranges studied. These modification factors reflect a value close to that expected for a fully aerobic response in this survival range. Growth delay studies in the SCCVII tumour provided similar results. Using a recently developed fluorescence activated cell sorting technique, which utilizes the in vivo pharmacokinetic and DNA binding properties of the bisbenzamide stain Hoechst 33342, the effect of Nicotinamide and/or Fluosol DA/Carbogen schedules on the occurrence of acute hypoxia was assessed. The results clearly show that Nicotinamide significantly reduces the amount of 'acute hypoxia', but has a lesser effect on 'chronic' hypoxic cells. However, combinations of Nicotinamide and Fluosol DA/Carbogen significantly increase the response of both 'acutely' and 'chronically hypoxic' cells. The results provide evidence that a combination of Nicotinamide and Fluosol DA/Carbogen can provide an effective way of reoxygenating both acutely and chronically hypoxic cells.