Is the novel guanine oxidative damage as important as 8-oxoguanine as a mutation source?

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K00558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Tokushima Bunri University
• Principal Investigator: Kino Katsuhito 徳島文理大学, 理工学部, 准教授 (70360534)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 損傷 / グアニン酸化損傷

Outline of Final Research Achievements

Under oxidative conditions, G→T and G→C point mutations have been observed, but the guanine oxidative damage, 8-oxoguanine, cannot cause G→C point mutations. The applicant reported that oxazolone, a guanine oxidative damage, can explain G→C point mutations, but it was recently found that oxazolone degrades gradually.
In this study, we investigate the structure determination, mutability, and repair reaction of X, a novel guanine oxidative damage discovered by the applicant. This study will explore the possibility that X could be a mutation source comparable to 8-oxoguanine.

Free Research Field

環境学・環境解析学・放射線化学物質影響科学

Academic Significance and Societal Importance of the Research Achievements

8oxoGはG→T点突然変異を引き起こすが、酸化条件で誘発されるG→C点突然変異をひきおこさないため、必ずやXによる突然変異機構の解明が、酸化による突然変異と8oxoGによる突然変異とのギャップを埋めることになると考えている。さらに、G→T点突然変異やG→C点突然変異が、がん遺伝子であるK-ras遺伝子やがん抑制遺伝子であるp53遺伝子でみられているように、Xに関する基礎的研究は、多段階突然変異による癌の生成機構の一端を解明できる波及効果を生むであろう。