Veszelovszky E, Thomsen L L, Li Z, Baguley B C
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Eur J Cancer. 1993;29A(3):404-8. doi: 10.1016/0959-8049(93)90396-w.
Antitumour agents such as flavone acetic acid, xanthenone acetic acid (XAA), 5,6-dimethylxanthenone-4-acetic acid and tumour necrosis factor-alpha, following single dose administration to mice with colon 38 adenocarcinomas, induce tumour haemorrhagic necrosis and an elevation in plasma nitrate. The relationship between these two effects has been studied using firstly a series of methyl-substituted XAA derivatives with varying antitumour activity, and secondly the inhibitors NG-monomethyl-L-arginine (NMMA), N-nitro-L-arginine (NNA) and canavanine, which affect nitric oxide synthesis. Elevation of plasma nitrate resulting from the oxidation of L-arginine by nitric oxide synthase is inhibited by NNA rather than by NMMA or canavanine. The results demonstrate that tumour necrosis can be induced in the absence of a significant elevation of plasma nitrate.
给患有结肠38腺癌的小鼠单次给药后，黄酮乙酸、呫吨酮乙酸（XAA）、5,6-二甲基呫吨酮-4-乙酸和肿瘤坏死因子-α等抗肿瘤药物会诱导肿瘤出血性坏死并使血浆硝酸盐水平升高。首先使用一系列具有不同抗肿瘤活性的甲基取代XAA衍生物，其次使用影响一氧化氮合成的抑制剂NG-单甲基-L-精氨酸（NMMA）、N-硝基-L-精氨酸（NNA）和刀豆氨酸，对这两种效应之间的关系进行了研究。一氧化氮合酶将L-精氨酸氧化导致的血浆硝酸盐升高受到NNA的抑制，而不是NMMA或刀豆氨酸的抑制。结果表明，在血浆硝酸盐没有显著升高的情况下也可诱导肿瘤坏死。
