Chromatin remodeling modulates radiosensitivity of the daughter cells derived from cell population exposed to low- and high-LET irradiation
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Ping Wang1,*, Dexiao Yuan1,*, Fei Guo1,*, Xiaoyan Chen1, Lin Zhu1, Hang Zhang1, Chen Wang1, Chunlin Shao1
1Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
*These authors have contributed equally to this work
Chunlin Shao, email: email@example.com
Keywords: radiosensitivity, LET-dependent, daughter cells, chromatin remodeling, heterochromatinization
Received: February 10, 2017 Accepted: March 28, 2017 Published: April 20, 2017
Radiation effects are dependent of linear energy transfer (LET), but it is still obscure whether the daughter cells (DCs) derived from irradiated population are radioresistance and much less the underlying mechanism. With the measurements of survival, proliferation and γH2AX foci, this study shows that the DCs from γ-ray irradiated cells (DCs-γ) became more radioresistant than its parent control without irradiation, but the radiosensitivity of DCs from α-particle irradiated cells (DCs-α) was not altered. After irradiation with equivalent doses of γ-rays and α-particles, the foci number of histone H3 lysine 9 dimethylation (H3K9me3) and the activity of histone deacetylase (HDAC) in DCs-γ was extensively higher than these in DCs-α and its parent control, indicating that a higher level of heterochromatin was formed in DCs-γ but not in DCs-α. Treatment of cells with SAHA (an inhibitor of HDAC) decreased the level of heterochromatin domains by inhibiting the expressions of H3K9m3 and HP-1a proteins and triggering the expression of acetylated core histone H3 (Ac-H3). When cells were treated with SAHA, the radioresistance phenotype of DCs-γ was eliminated so that the radiosensitivities of DCs-γ, DCs-α and their parent cells approached to same levels. Our current results reveal that γ-rays but not α-particles could induce chromatin remodeling and heterochromatinization which results in the occurrence of radioresistance of DCs, indicating that the combination treatment of irradiation and HDAC inhibitor could serve as a potential cancer therapy strategy, especially for the fraction radiotherapy of low-LET irradiation.
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