Dynamic imaging analysis reveals Auger electron-emitting radio-cisplatin induces DNA damage depending on the cell cycle.

Autor: Obata H; Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan; Department of Molecular Imaging and Theranostics, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan; Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan., Kurimasa A; Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi 983-8536, Japan. Electronic address: kurimasa@tohoku-mpu.ac.jp., Muraoka T; Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi 983-8536, Japan., Tsuji AB; Department of Molecular Imaging and Theranostics, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. Electronic address: tsuji.atsushi@qst.go.jp., Kondo K; Department of Electrical Engineering and Computer Science, Tottori University, 4-101 Koyama-Minami, Tottori-shi, Tottori, 680-8550, Japan., Kuwahara Y; Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi 983-8536, Japan., Minegishi K; Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Nagatsu K; Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Ogawa M; Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan., Zhang MR; Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2022 Dec 31; Vol. 637, pp. 286-293. Date of Electronic Publication: 2022 Nov 12.
DOI: 10.1016/j.bbrc.2022.11.016
Abstrakt: Auger electrons can induce nanoscale physiochemical damage to DNA. The present study reports a sequential and systematic evaluation of the relationship between DNA damage such as double-strand breaks (DSBs) and the cell cycle for the Auger electron-emitting agent radiolabeled cisplatin with DNA binding ability. For dynamic imaging analysis, we used U2OS-derived cancer cells expressing two fluorescent fusion proteins: tumor-suppressor p53 binding protein 1 with a green fluorescent protein (53BP1-EGFP) and proliferating cell nuclear antigen with a red fluorescent protein (PCNA-DsRed). Time-lapse images of the cells were quantitatively analyzed using the ImageJ software with the deepImageJ plugin and the Google Colaboratory platform. From the middle-to-late G1 phase, around the G1-to-S phase transition, we found increased 53BP1 foci in cells treated with the radio-cisplatin. The radio-cisplatin caused significantly more DSBs than the nonradioactive cisplatin and saline in the G1 phase but not in the other phases. These results indicate that Auger electron-induced DNA damage, including DSBs, depends on the cell cycle. The G1 phase, which is associated with low DNA repair capacity and high radiosensitivity, is a promising target; thus, combining radiolabeled cisplatin with agents that arrest cells in the G1 phase could improve the DNA-damaging effect of Auger electrons and their therapeutic efficacy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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