Persistent oxidative stress in human colorectal carcinoma, but not in adenoma
Persistent oxidative stress in human colorectal carcinoma, but not in adenoma
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DOI：
10.1016/s0891-5849(99)00087-8
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发表时间：
1999-08-01
影响因子：
7.4
通讯作者：
Imamura, M
中科院分区：
文献类型：
--
作者：
Kondo, S;Toyokuni, S;Imamura, M
很少有研究关注活性氧在肿瘤细胞代谢中的潜在作用。在这里，我们研究了人类结直肠腺癌和腺瘤，以确定是否在体内对癌细胞施加氧化应激，并使用针对8-羟基-2 '-脱氧鸟苷（8-OHdG）、4-羟基-2-壬烯醛（HNE）修饰蛋白和3-硝基-L-酪氨酸（3-WT）的特异性抗体来确定氧化应激和细胞增殖之间是否存在关联。通过免疫组化以及基于高效液相色谱（HPLC）的8-OHdG测定，在癌细胞中观察到更高水平的DNA和蛋白质氧化修饰，但在腺瘤细胞中没有观察到。增殖细胞核抗原阳性细胞的比例在腺癌与8-OHdG和3-NT的染色强度。此外，从癌细胞中提取的蛋白质的Western印迹分析揭示了几个特定的蛋白质修饰的HNE或过氧亚硝酸盐。因此，我们得出结论，结直肠癌，而不是腺瘤细胞，暴露于更多的氧化应激比相应的非肿瘤上皮细胞，无论临床分期和组织学，并进一步在癌细胞的氧化应激可能会刺激细胞增殖。(C)1999 Elsevier Science Inc.
Few studies have been conducted focusing on a potential role of reactive oxygen species in tumor cell metabolism. Here we studied human colorectal adenocarcinomas and adenomas to determine whether oxidative stress is imposed on cancer cells in vivo and used specific antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE)-modified proteins, and 3-nitro-L-tyrosine (3-WT) to determine whether there is an association between oxidative stress and cellular proliferation. Higher levels of oxidative modifications in DNA and proteins were observed in carcinoma cells, but not in adenoma cells, than in the corresponding nontumorous epithelial cells by immunohistochemistry as well as high-performance liquid chromatography (HPLC)-based 8-OHdG determination. The fraction of proliferating cell nuclear antigen-positive cells was proportionally associated in adenocarcinomas with the staining intensities of 8-OHdG and 3-NT. Furthermore, Western blot analysis of the proteins extracted from carcinoma cells revealed several specific proteins modified by HNE or peroxynitrite. Thus we concluded that colorectal carcinoma, but not adenoma cells, are exposed to more oxidative stress than their corresponding nontumorous epithelial cells, regardless of clinical stage and histology, and further that the oxidative stress in carcinoma cells might stimulate cellular proliferation. (C) 1999 Elsevier Science Inc.