title: Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation.
abstract: Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research.
authors.affiliation: Gansu Key Laboratory of Space Radiobiology & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Xurui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Gansu Key Laboratory of Space Radiobiology & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.
authors.forename: Caiyong
authors.initials: C
authors.lastname: Ye
authors.affiliation: Gansu Key Laboratory of Space Radiobiology & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Gansu Key Laboratory of Space Radiobiology & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wei
authors.affiliation: Gansu Key Laboratory of Space Radiobiology & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.
authors.forename: Burong
authors.initials: B
authors.lastname: Hu
authors.affiliation: Gansu Key Laboratory of Space Radiobiology & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.
authors.forename: Jufang
authors.initials: J
authors.lastname: Wang
mesh_terms: D002244:Carbon; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics* / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D006801:Humans; D018499:Linear Energy Transfer; D016615:Telomere; D014965:X-Rays; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D002244:Carbon; D001616:beta-Galactosidase