Gibby E M, Cohen G M
Br J Cancer. 1984 May;49(5):645-51. doi: 10.1038/bjc.1984.100.
The metabolism of 1-naphthol, a model phenolic substrate, to its glucuronic acid and sulphate ester conjugates has been studied in short-term organ cultures of normal human colon and tumour tissue, subcellular fractions of these tissues, human colonic tumour cell lines and human colonic tumour xenografts. Normal colonic tissue, in short-term organ culture, formed more 1-naphthyl sulphate than glucuronic acid conjugates. In contrast the colonic tumours, under the same conditions, produced more 1-naphthyl beta-D-glucuronide than 1-naphthyl sulphate. A marked interindividual variation in sulphate ester and glucuronic acid conjugation was noted in both normal and tumorous colon. The conjugation of 1-naphthol was also investigated, using subcellular fractions, where the metabolism found with normal colon reflected that observed utilizing short-term organ culture, but that from colonic tumour samples did not. Cell lines derived from human colonic adenocarcinomas metabolised 1-naphthol almost exclusively to its glucuronic acid conjugate. Xenografts derived from human colonic tumours formed similar conjugates to surgical samples in culture. Thus somewhat different results were obtained dependent on the experimental model chosen. However, in all colonic tumour systems studied, when the cells remained intact and where tissue architecture was maintained, 1-naphthol was metabolised predominantly to its glucuronic acid conjugate.
在正常人结肠和肿瘤组织的短期器官培养物、这些组织的亚细胞组分、人结肠肿瘤细胞系及人结肠肿瘤异种移植模型中,对作为酚类底物模型的1-萘酚代谢生成其葡萄糖醛酸和硫酸酯共轭物的情况进行了研究。在短期器官培养中,正常结肠组织生成的1-萘基硫酸酯比葡萄糖醛酸共轭物更多。相比之下,在相同条件下,结肠肿瘤生成的1-萘基β-D-葡萄糖醛酸比1-萘基硫酸酯更多。在正常和肿瘤结肠中均观察到硫酸酯和葡萄糖醛酸结合存在明显的个体间差异。还使用亚细胞组分研究了1-萘酚的结合情况,其中正常结肠的代谢情况与利用短期器官培养所观察到的一致,但结肠肿瘤样本的代谢情况并非如此。源自人结肠腺癌的细胞系将1-萘酚几乎完全代谢为其葡萄糖醛酸共轭物。源自人结肠肿瘤的异种移植模型在培养中形成的共轭物与手术样本相似。因此,根据所选实验模型会得到 somewhat different results(此处原文有误,推测可能是“somewhat different results”,意为“有些不同的结果”)。然而,在所有研究的结肠肿瘤系统中,当细胞保持完整且组织结构得以维持时,1-萘酚主要代谢为其葡萄糖醛酸共轭物。