DNA damage response in a 2D-culture model by diffusing alpha-emitters radiation therapy (Alpha-DaRT).

Autor: Nojima H; Department of Dental Radiology and Radiation Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan., Kaida A; Department of Dental Radiology and Radiation Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan., Matsuya Y; Nuclear Science and Engineering Center, Japan Atomic Energy Agency, 2-4 Shirakata, Tokai, Ibaraki, 319-1195, Japan.; Faculty of Health Sciences, Hokkaido University, Kita-12 Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan., Uo M; Department of Advanced Biomaterials, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan., Yoshimura RI; Department of Radiation Therapeutics and Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan., Arazi L; Unit of Nuclear Engineering, Faculty of Engineering Sciences, Ben-Gurion University of the Negev, P.O.B. 653, 8410501, Be'er-Sheva, Israel., Miura M; Department of Dental Radiology and Radiation Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan. masa.mdth@tmd.ac.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 May 20; Vol. 14 (1), pp. 11468. Date of Electronic Publication: 2024 May 20.
DOI: 10.1038/s41598-024-62071-6
Abstrakt: Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique method, in which interstitial sources carrying 224 Ra release a chain of short-lived daughter atoms from their surface. Although DNA damage response (DDR) is crucial to inducing cell death after irradiation, how the DDR occurs during Alpha-DaRT treatment has not yet been explored. In this study, we temporo-spatially characterized DDR such as kinetics of DNA double-strand breaks (DSBs) and cell cycle, in two-dimensional (2D) culture conditions qualitatively mimicking Alpha-DaRT treatments, by employing HeLa cells expressing the Fucci cell cycle-visualizing system. The distribution of the alpha-particle pits detected by a plastic nuclear track detector, CR-39, strongly correlated with γH2AX staining, a marker of DSBs, around the 224 Ra source, but the area of G2 arrested cells was more widely spread 24 h from the start of the exposure. Thereafter, close time-lapse observation revealed varying cell cycle kinetics, depending on the distance from the source. A medium containing daughter nuclides prepared from 224 Ra sources allowed us to estimate the radiation dose after 24 h of exposure, and determine surviving fractions. The present experimental model revealed for the first time temporo-spatial information of DDR occurring around the source in its early stages.
(© 2024. The Author(s).)
Databáze: MEDLINE
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