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

Nojima, Hitomi*; Kaida, Atsushi*; Matsuya, Yusuke  ; Uo, Motohiro*; Yoshimura, Ryoichi*; Arazi, L.*; Miura, Masahiko*

Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique radiotherapy that uses seeds emitting alpha particles placed in solid tumors to kill cancer cells surrounding the seeds. Although the DNA damage response is an important cellular response that determines cell death after radiation; however, how DNA damage response occurs during Alpha-DaRT treatment has not yet been explored. In this study, we measured the spatiotemporal characteristics of the DNA damage response, including the number of DNA double-strand breaks and G2 arrest, during Alpha-DaRT treatment by cell experiments using HeLa cells expressing the Fucci cell cycle visualization system. As a result, we found a strong correlation between the number of alpha particles detected by solid-state track detector CR-39 and -H2AX staining, a marker for detecting DNA damage, and that the area of G2-arrested cells spread over a wider area up to 24 hours. In addition, time-lapse observations revealed that cell cycle dynamics change depending on the distance from the seed. The experimental model in this study revealed for the first time the spatiotemporal information of the DNA damage response around the seed during Alpha-DaRT treatment.