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

被引：0

作者：

Nojima, Hitomi ^{[1
]}

Kaida, Atsushi ^{[1
]}

Matsuya, Yusuke ^{[2
,3
]}

Uo, Motohiro ^{[4
]}

Yoshimura, Ryo-ichi ^{[5
]}

Arazi, Lior ^{[6
]}

Miura, Masahiko ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Dent Radiol & Radiat Oncol, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138549, Japan

[2] Japan Atom Energy Agcy, Nucl Sci & Engn Ctr, 2-4 Shirakata, Tokai, Ibaraki 3191195, Japan

[3] Hokkaido Univ, Fac Hlth Sci, Kita-12 Nishi-5,Kita Ku, Sapporo, Hokkaido 0600812, Japan

[4] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Adv Biomat, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138549, Japan

[5] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Radiat Therapeut & Oncol, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138549, Japan

[6] Ben Gurion Univ Negev, Fac Engn Sci, Unit Nucl Engn, POB 653, IL-8410501 Beer Sheva, Israel

来源：

SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期

基金：

日本学术振兴会;

关键词：

INFORMATION-FLOW; BRAIN; OXYTOCIN; BEHAVIOR;

D O I：

10.1038/s41598-024-62071-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique method, in which interstitial sources carrying 224Ra 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 gamma H2AX staining, a marker of DSBs, around the 224Ra 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 224Ra 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.

引用

页数：13

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[21] SLEAP: A deep learning system for multi-animal pose tracking [J].