Tracer studies of potential radiosensitizing agents: tetrasodium 2-14C-methyl-1:4-naphthohydroquinone diphosphate.
Tracer studies of potential radiosensitizing agents: tetrasodium 2-14C-methyl-1:4-naphthohydroquinone diphosphate.
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DOI：
10.1038/bjc.1956.69
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发表时间：
1956-09
影响因子：
8.8
通讯作者：
MAXWELL, D R
中科院分区：
文献类型：
--
作者：
MARRIAN, D H;MAXWELL, D R
如果能找到一种无毒的化合物，它可以选择性地集中在肿瘤组织中，而且还可以增加细胞对X射线的敏感性，那么它可能用于治疗恶性肿瘤。多年来，这些实验室一直在关注放射增敏剂的研究，最初的研究主要涉及二磷酸四异丙基2-甲基-I：4-萘氢醌（I）。由于其易于脱磷酸化和氧化为2-甲基-1：4-萘醌，它是一种合成维生素K替代品（Synkavit），但它也影响鸡成纤维细胞培养物中的有丝分裂（Mitchell和Simon-Reuss，1947）。它增加了X射线照射对组织培养物的抗有丝分裂和染色体断裂作用（Mitchell和Simon-Reuss，1947，1952 a，1952 b），也增加了携带步行者癌的大鼠的X射线肿瘤消退（Mitchell，1954）。对于不能手术的肺癌，经X线治疗后，患者的生存时间也有少量但有效的延长（Mitchell，1953）。此外，Mitchell（1954）观察到，在将（I）注射到大鼠体内后，如果解剖并用碱性过氧化氢处理，一些内脏在紫外光下显示出明亮的黄色荧光;在肿瘤的生长边缘上荧光特别强。这似乎表明源自（I）的2-甲基-I：4-萘醌-2：3-氧化物（II）在局部蓄积。因此，通过研究在甲基中用14 C标记的（I）的代谢，寻求关于可能的选择性浓度的进一步信息。
IF a non-toxic compound could be found which would concentrate selectively in tumour tissue and which would also increase the sensitivity of cells towards X-rays, it might be of use in the treatment of malignancy. This search for a radio-sensitizer has been the concern of these laboratories for a number of years, and initial studies have been mainly concerned with tetrasodium 2-methyl-I: 4-naphthohydroquinone diphosphate (I).The compound has several biological actions of interest. It is a synthetic Vitamin K substitute (Synkavit) by virtue of its ready dephosphorylation and oxidation to 2-methyl-1: 4-naphthoquinone, but it also affects mitoses in cultures of chick fibroblasts (Mitchell and Simon-Reuss, 1947). It increases the antimitotic and chromosome fragmentation effects of X-irradiation on tissue cultures (Mitchell anid Simon-Reuss, 1947, 1952a, 1952b) and also increases tumour retrogression by X-rays in rats bearing a Walker carcinoma (Mitchell, 1954). A small but useful increase in the survival time of patients undergoing X-ray therapy for inoperable carcinoma of the lung has also been reported (Mitchell, 1953). Furthermore, Mitchell (1954) has observed that after an injection of (I) into the rat, some internal organs, if dissected and treated with alkaline hydrogen peroxide, show a brilliant yellow fluorescence in ultra-violet light; the fluorescence is especially strong on the growing edge of the tumour. It seemed likely that this indicated local accumulations of 2-methyl-I: 4-naphthoquinone-2: 3-oxide (II) derived from (I). Further information on possible selective concentration was therefore sought by studying themetabolism of (I) labelled with 14C in the methyl group.