| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
An oxidized form of guanine, 8-oxoGua, is known to have a potential to induce genetic mutations, thereby causing carcinogenesis. Mammalian cells hence have various mechanisms to eliminate 8-oxoGua in DNA and nucleotide pools. Since MutT-related enzymes, MTH1 and NUDT5, can hydrolyze 8-oxoGua-containing nucleotides in nucleotide pools, the expressions of MTH1 and NUDT5 are likely to be involved in controlling oxidation-induced carcinogenesis. In the present study, we examined the expressions of 8-oxoGua, MTH1 and NUDT5 in human normal keratinocytes and human oral squamous carcinoma cells treated with H_2O_2. As a result, the immunofluorescent study demonstrated that the localization of 8-oxo-dGTP changed from cytoplasm to nucleus in the treatment with H_2O_2. The Western blotting analysis as well as RT-PCR revealed that H_2O_2 enhanced the expression of NUDT5, but not MTH1, in normal keratinocytes. The increased NUDT5 proteins were also detected in the nuclear extracts of keratinocytes treated with H_2O_2. In contrast, H_2O_2 had no effects on the expressions of NUDT5 and MTH1 in squamous carcinoma cells. NUDT5 may thus be involved in preventing the carcinogenic mutations in keratinocytes under oxidative stress.
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