Iida T, Furuta A, Kawashima M, Nishida J, Nakabeppu Y, Iwaki T
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University 60, Fukuoka, 812-8582, Japan.
Neuro Oncol. 2001 Apr;3(2):73-81. doi: 10.1093/neuonc/3.2.73.
Oxidative DNA damage generated by an attack of reactive oxygen species causes mutation or cell death that may lead to various diseases and may be related to initiation or progression of carcinogenesis. 8-Oxo-2'-deoxyguanosine (8-oxo-dG) is a major oxidative DNA damage product that can result in mutation, and hMTH1, human MutT homolog protein 1, has been identified as an enzyme that hydrolyzes 8-oxo-dGTP to the monophosphate, thus preventing accumulation of 8-oxo-dG in DNA. With immunohistochemical approaches, we investigated accumulation of 8-oxo-dG and expression of hMTH1 in brain tumor tissues obtained from surgical and autopsy cases, including 42 neuroepithelial tumors, 5 meningiomas, 2 metastatic brain tumors, and 1 schwannoma. 8-Oxo-dG accumulation and hMTH1 expression were increased in various brain tumors. Nuclei of brain tumor cells were immunoreactive for 8-oxo-dG in all cases. In most cases, both nuclei and cytoplasm of the tumor cells were immunoreactive for hMTH1. Both 8-oxo-dG accumulation and hMTH1 expression were most evident in high-grade gliomas, indicating that oxidative stress was high in these gliomas. Thus, the defense mechanism against such oxidative stress may be enhanced as well. These results suggest that oxidative stress may play a role in tumor progression.
活性氧攻击产生的氧化性DNA损伤会导致突变或细胞死亡，这可能引发各种疾病，并可能与癌症发生的起始或进展有关。8-氧代-2'-脱氧鸟苷（8-氧代-dG）是一种主要的氧化性DNA损伤产物，可导致突变，而人MutT同源蛋白1（hMTH1）已被鉴定为一种将8-氧代-dGTP水解为单磷酸的酶，从而防止8-氧代-dG在DNA中积累。通过免疫组织化学方法，我们研究了从手术和尸检病例中获取的脑肿瘤组织中8-氧代-dG的积累和hMTH1的表达，这些病例包括42例神经上皮肿瘤、5例脑膜瘤、2例脑转移瘤和1例神经鞘瘤。在各种脑肿瘤中，8-氧代-dG的积累和hMTH1的表达均增加。在所有病例中，脑肿瘤细胞的细胞核对8-氧代-dG呈免疫反应性。在大多数病例中，肿瘤细胞的细胞核和细胞质对hMTH1均呈免疫反应性。8-氧代-dG的积累和hMTH1的表达在高级别胶质瘤中最为明显，表明这些胶质瘤中的氧化应激较高。因此，针对这种氧化应激的防御机制可能也会增强。这些结果表明氧化应激可能在肿瘤进展中起作用。
