SYNERGISTIC KILLING OF EHRLICH ASCITES CARCINOMA CELLS BY ASCORBATE AND 3-AMINO-1,2,4-TRIAZOLE
SYNERGISTIC KILLING OF EHRLICH ASCITES CARCINOMA CELLS BY ASCORBATE AND 3-AMINO-1,2,4-TRIAZOLE
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DOI：
10.1159/000224465
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发表时间：
1969-01-01
期刊：
影响因子：
3.5
通讯作者：
BURK, D
中科院分区：
文献类型：
--
作者：
BENADE, L;HOWARD, T;BURK, D
本研究表明抗坏血酸（维生素C）对体外埃利希腹水癌细胞具有高毒性或致死性。如果同时服用3-氨基- 1,2,4，-三唑（ATA），这种毒性会大大增加。单独给药时，除了特异性抑制过氧化氢酶（h2o2分解）活性外，ATA对癌细胞几乎是无害的。抗坏血酸的细胞杀伤特性被认为主要是由于抗坏血酸被细胞氧化后在细胞内产生有毒的过氧化氢。ATA的增效作用被认为是由于它抑制过氧化氢酶，从而降低或破坏癌细胞有效解毒h2o的能力。先前的研究已经证实，与大多数其他癌细胞一样，埃利希腹水细胞的数据激光活性[13]通常比类似的正常细胞低10-100倍。因此，给定浓度的ATA可以有效结合肿瘤细胞的所有过氧化氢酶，而不会对类似正常细胞的过氧化氢酶活性造成如此有效的损害。抗坏血酸和ATA作为潜在的抗癌药物的巨大优势在于，它们像青霉素一样，对正常身体组织明显无毒，并且它们可以以极大剂量（高达5克/公斤或更多克/公斤）施用于动物而没有明显的有害药理作用。
The present study shows that ascorbate (vitamin C) is highly toxic or lethal to Ehrlich ascites carcinoma cells in vitro. This toxicity is greatly increased synergistically by concomitant administration of 3-amino-1, 2, 4,-triazole (ATA). ATA, when given alone, is virtually harmless to the cancer cells, except for specifically inhibiting their catalase (H20 2-decomposing) activity. The cytocidal property of the ascorbate is believed to be due in major part to the intracellular genera tion of toxic hydrogen peroxide produced upon oxidation of the as corbate by the cells. The synergistic enhancement by ATA is believed to be due to its inhibition of the enzyme catalase, thereby decreasing or destroying the ability of the cancer cells to detoxify the H20 2effec tively. Previous studies have established that Ehrlich ascites cells, in common with most other cancer cells, are ordinarily very low in cata lase activity [13] in contrast to comparable normal cells, by a factor of 10-100 fold [1]. Thus, a given concentration of ATA can effectively bind all the catalase of a neoplastic cell while providing no such effec tive impairment of the catalatic activities of comparable normal cells. The great advantage that ascorbate and ATA possess as potential anticancer agents is that they are, like penicillin, remarkably nontoxic to normal body tissues, and they may be administered to animals in extremely large doses (up to 5 or more gm/kg) without notable harm ful pharmacological effects.