Accumulation of 8-oxo-2 '-deoxyguanosine and increased expression of hMTH1protein in brain tumors

Oxidative DNA damage generated by an attack of reactive oxygen species caus es mutation or cell death that may lead to various diseases and may be rela ted to initiation or progression of carcinogenesis. 8-Oxo-2'-deoxyguanosine (8-oxo-dG) is a major oxidative DNA damage product that can result in muta tion, and hMTH1, human MutT homolog protein 1, has been identified as an en zyme that hydrolyzes 8-oxo-dGTP to the monophosphate, thus preventing accum ulation of 8-oxo-dG in DNA. With immunohistochemical approaches, we investi gated accumulation of 8-oxo-dG and expression of hMTH1 in brain tumor tissu es obtained from surgical and autopsy cases, including 42 neuroepithelial t umors, 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 immunoreac tive for hMTH1. Both 8-oxo-dG accumulation and hMTH1 expression were most e vident in high-grade gliomas, indicating that oxidative stress was high in these gliomas. Thus, the defense mechanism against such oxidative stress ma y be enhanced as well. These results suggest that oxidative stress may play a role in tumor progression.