Radiation-induced impacts on mitochondrial DNA and the transgenerational genomic instability

Seino, Ryosuke; Kubo, Haruka; Nishikubo, Kai; Fukunaga, Hisanori

Radiation-induced impacts on mitochondrial DNA and the transgenerational genomic instability

Seino, Ryosuke; Kubo, Haruka; Nishikubo, Kai et al.

Environment International, 2025, 196, 109315

Permalink : https://hdl.handle.net/2115/93990

このアイテムのアクセス数:171件（2026-08-16 20:02 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/93990
タイトル	Radiation-induced impacts on mitochondrial DNA and the transgenerational genomic instability
著者	Seino, Ryosuke ; Kubo, Haruka ; Nishikubo, Kai ; Fukunaga, Hisanori
e-Rad_Researcher 61006194 著者名 Seino, Ryosuke
著者名 Kubo, Haruka
著者名 Nishikubo, Kai
e-Rad_Researcher 50781267 著者名 Fukunaga, Hisanori
言語	英語
キーワード	DNA copy number variation
	genomic instability
	hereditary effect
	mitochondrial DNA
	radiation
発行日	2025-02-02
出版者	Elsevier
収録物名	Environment International
巻(号)	196
ページ	109315
抄録	Background Mitochondrial genomes are dynamically evolving and are shaped by somatic mutation and selection throughout the female germline. In this study, we investigated the radiation-induced impacts on mitochondrial DNA in vitro and in vivo, as well as the transgenerational inheritance. Methods Human cervical cancer HeLa cells and telomerase-immortalized normal fibroblast BJ1-hTERT cells were exposed to X-rays at 0.5–8 Gy. Also, we exposed 8-week-old female C57BL/6N mice to a single whole-body dose of 2 Gy of X-rays and mated them with healthy males 1 day after irradiation. We extracted DNA from the irradiated cells, female mice, and the 2-week-old pups, then examined the mitochondrial DNA copy numbers (mtDNAcns) and radiation-induced damage by real-time quantitative PCR. Results The mtDNAcn levels in cells increased and the intact copy ratios decreased 24 h after irradiation, resulting in the delayed shift of heteroplasmy. Also, the peripheral blood-derived mtDNAcn levels in irradiated females increased 1 day after irradiation and the intact copy rates decreased, supporting the results in vitro. Furthermore, whole blood-derived mtDNAcn levels decreased in 2-week-old pups born from irradiated mothers, indicating the mitochondrial genomic instability. Discussion We found the delayed induction of mtDNA damage in human cancer and noncancerous cells after irradiation, as well as the same trend in mice. Furthermore, to our knowledge, this is first to demonstrate the hereditary effects of radiation on the regulation of mitochondrial genome. These provide novel insights into the significance of radiation protection and preventive medicine for not only pre-pregnancy females but also the next generation.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
権利情報	© 2025 The Author(s). Published by Elsevier Ltd.
PISSN	0160-4120
EISSN	1873-6750
NCID	AA00180393
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1016/j.envint.2025.109315