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Neuropathology |
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences (T.Ii., A.F., M.K., T.Iw.), Department of Biochemistry, Medical Institute of Bioregulation (J.N., Y.N.), Kyushu University, Fukuoka, 812-8582, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, 105-0011, Japan (T.Ii., A.F., Y.N., T.Iw.)
1 Address correspondence and reprint requests to Dr. Takashi Iida, Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University 60, Fukuoka, 812-8582, Japan.
Abstract
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.
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