RADIOSENSITIZATION BY NICOTINAMIDE INVIVO - A GREATER ENHANCEMENT OF TUMOR DAMAGE COMPARED TO THAT OF NORMAL-TISSUES
RADIOSENSITIZATION BY NICOTINAMIDE INVIVO - A GREATER ENHANCEMENT OF TUMOR DAMAGE COMPARED TO THAT OF NORMAL-TISSUES
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DOI：
10.2307/3577048
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发表时间：
1987-03-01
影响因子：
3.4
通讯作者：
BROWN, JM
中科院分区：
文献类型：
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作者：
HORSMAN, MR;CHAPLIN, DJ;BROWN, JM
在这份报告中，我们描述了烟酰胺对肿瘤和正常组织放射增敏的各个方面。C3 H小鼠单次注射烟酰胺的LD 50为2050 mg/kg。当将大的非致死剂量（1000 mg/kg）注射到荷瘤小鼠中时，注射后30-60 min达到血浆和肿瘤水平峰值，并以约3 h的半衰期衰减。当在照射前至少1小时注射时，该剂量的烟酰胺增强了三种不同肿瘤模型（EMT 6、刘易斯肺和RIF-1）中的辐射诱导的细胞杀伤，并产生1.2至1.7的增强比（ER）。EMT 6肿瘤中的ER依赖于注射的烟酰胺剂量，但即使在低至LD 50值的25%的剂量下，仍可以观察到ER大于1.5。在两个正常组织测定（空肠隐窝细胞存活和平均皮肤反应）ER小于1.2。这些结果以及人体可以耐受高水平的事实表明，烟酰胺或结构相关的化合物可能是临床试验开发的可能候选物。
In this report we describe various aspects of tumor and normal tissue radiosensitization by nicotinamide. The LD50 for a single injection of nicotinamide in C3H mice was found to be 2050 mg/kg. When a large nonlethal dose (1000 mg/kg) was injected into tumor-bearing mice, peak plasma and tumor levels were reached 30-60 min after injection and decayed with a half-life of about 3 h. This dose of nicotinamide enhanced radiation-induced cell killing in three different tumor models (EMT6, Lewis Lung, and RIF-1) when injected at least 1 h before irradiation and produced enhancement ratios (ERs) of between 1.2 and 1.7. The ER in the EMT6 tumor was dependent on the dose of nicotinamide injected, but even at doses as low as 25% of the LD50 value in ER greater than 1.5 could still be observed. In two normal tissue assays (jejunum crypt cell survival and mean skin reaction) ERs of less than 1.2 were obtained. These results, and the fact that high levels can be tolerated in humans, suggest that nicotinamide, or a structurally related compound, could be a likely candidate for development in clinical trials.