The Involvement of PLDR inhibition and unreparable DNA double-strand breaks as a basis for radiotherapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K19855
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Hamamatsu University School of Medicine (2019); Yokohama City University (2018); Juntendo University (2016-2017)
• Principal Investigator: Sekihara Kazumasa 浜松医科大学, 医学部, 助教 (20761662)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: DNA修復 / 潜在的致死損傷回復 / クロマチンリモデリング

Outline of Final Research Achievements

Using the measurement of unrepairable DNA double strand breaks(DNA-DSBs) as a indicator, we examined how inhibition of potentially lethal damage recovery(PLDR) affects the production of unrepairable DNA-DSBs by radiation. The inhibition of PLDR increased the number of unrepairable DNA-DSB. But there was no significant difference in the number of DSBs immediately after irradiation. We next tested whether histone demethylation inhibitors enhance the antitumor effects of radiation and anticancer agents in human prostate cancer and oral cancer cell lines. In both cell lines, the treatment with a histone demethylation inhibitor inhibited cell growth in a dose dependent manner. Furthermore, it was suggested that JIB-04 enhances the antitumor effect of radiation and is associated with DNA repair in prostate cancer.

Free Research Field

放射線生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は長年期待されていたPLDR阻害メカニズム解明に対して、最新の分子生物学を用いて挑む野心的な試みであり、放射線や抗がん剤によるがん治療に対する新しい考え方の基盤となる。それと同時に最近のホットトピックである、クロマチン構造の変化とDSB修復の関連性のより深い理解にも貢献できる。特に修復不能なDSBとの関係を検証するのは世界初の試みである。