2011 Fiscal Year Final Research Report
Study on treatment for epigenetic alternation of oral mucosa keratinocytes in radiotherapy-and chemotherapy-induced oral mucositis.
| Project/Area Number |
22791997
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Surgical dentistry
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | 口腔外科学一般 |
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| Research Abstract |
Other than the direct effect of ionizing radiation and cytotoxic effect of chemotherapeutic agent to oral cancer, damage of DNA in healthy oral keratinocyte is thought by acquired interruption of genetic expression ; epigenetic alternation in the radiation and chemotherapy-induced oral mucositis. The effect of histone deacetylase(HDAC) inhibitor is studied for epigenetic therapy. In this study, the effect of trichostatin A, having a suppressing effect of damaged cell DNA by X-ray irradiation and chemotherapeutic agent, was investigated using monolayer culture system of oral keratinocyte in serum free medium. Oral mucosa samples were taken from seven subjects receiving from minor oral surgery. From these samples, only two cell lines were able to establish and used for this experiment. Cisplatin(CDDP) was applied in the medium and colony forming assay was done. Result showed that 100μM of CDDP inhibited cell growth. Next growth-arrest assay was done by trichostatin A. In the first study, 50% of growth inhibition was seen when 100nM of trichostatin A was applied in the medium. But growth inhibitory ratio was not stable at a rate of 70 to 80 percent in the second and third study, optimum concentration of trichostatin A was not obtained. After applying 100nm of trichostatin A in the medium and cultured for 24 hours, cells were irradiated at 2Gy of X-ray. Colony forming assay was done after irradiation but no colonies were seen. After applying the same concentration of trichostatin A, CDDP was administered in the medium and cultured for 24 hours, then colony forming assay was done. Result was the same as assay of X-ray irradiation and no colonies were seen. Unfortunately, sample numbers were too little to continue this experiment. I supposed to need to reconsider the concentration of trichostatin A and usage of other HDAC inhibitor.
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