Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation

• Published in: PloS one 2016-05, Vol.11 (5), p.e0155725-e0155725
• Main Authors: Zhang, Xurui, Ye, Caiyong, Sun, Fang, Wei, Wenjun, Hu, Burong, Wang, Jufang
• Format: Article
• Language: English
• Subjects: Apoptosis; beta-Galactosidase - metabolism; Biological effects; Biology; Biology and life sciences; Cancer; Carbon; Cell aging; Cell cycle; Cell Line, Tumor; Cell proliferation; Cellular Senescence - genetics; Cellular Senescence - radiation effects; Comparative analysis; Complexity; Complications and side effects; Deoxyribonucleic acid; DNA; DNA Damage; DNA repair; Dose-Response Relationship, Radiation; Drug dosages; Extraterrestrial radiation; Fibroblasts; Galactosidase; Genetic aspects; Heavy Ions; Humans; Ion beams; Ionizing radiation; Ions; Kinases; Laboratories; Linear Energy Transfer; Medicine; Medicine and Health Sciences; Melanoma; Penicillin; Physical Sciences; Physics; Physiological aspects; Proteins; Radiation; Radiation damage; Radiation research; Relative biological effectiveness (RBE); Repair; Research and Analysis Methods; Senescence; Skin cancer; Telomere; X rays; β-Galactosidase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0155725

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.