Cardiovascular complication and DNA damage in radiation therapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10449
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Fukushima Medical University
• Principal Investigator: Ishida Takafumi 福島県立医科大学, 医学部, 教授 (40346482)
• Co-Investigator(Kenkyū-buntansha): 石田 万里 広島大学, 医系科学研究科(医), 准教授 (30359898) ; 鈴木 義行 福島県立医科大学, 医学部, 教授 (60334116)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: DNA損傷

Outline of Final Research Achievements

Radiotherapy for head and neck cancer increases the risk of exacerbation of carotid atherosclerotic lesions and thereby that of stroke. This study examined the effect of radiation on DNA damage/DNA damage response in patients receiving radiotherapy for head and neck cancer. Peripheral mononuclear cells from patients with head and neck cancers were isolated before and after radiotherapy. gammaH2AX were measured as a marker for DNA double-strand breaks by immunofluorescent study, and dicentric chromosomes were quantified as a marker for chromosome aberration by FISH. Both gammaH2AX and dicentric chromosomes in mononuclear cells were increased after radiotherapy. The expression of inflammatory cytokines were also increased. Immunoblot showed NF-kappaB activity was increased after radiotherapy. Thus, DNA damage and DNA damage response may mediate acceleration of atherosclerosis in patients with head and neck cancer by radiotherapy.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

放射線治療による動脈硬化性病変の増悪にDNA損傷あるいはDNA損傷応答が関与することが示唆された。この経路を定量することにより、動脈硬化性病変が増悪する患者を予知する手がかりとなり得ることが示唆された。またこの経路を標的とすることが、放射線治療の副作用を最小限に留めつつ、その恩恵を最大限に享受する方策を作るうえで重要な手がかりとなり得る。