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Genome Sequencing Unveils Mutational Impacts of Radiation on Mammalian Cells Recent release of the waste water from Japan's Fukushima nuclear disaster stirred apprehension regarding the health implications of radiation exposure. Classified as a Group 1 carcinogen, ionizing radiation has long been associated with various cancers and genetic disorders, as evidenced by survivors and descendants of atomic bombings and the Chernobyl disaster. Despite much smaller amount, we remain consistently exposed to low levels of radiation in everyday life and medical procedures. Radiation, whether in the form of high-energy particles or electromagnetic waves, is conventionally known to break our cellular DNA, leading to cancer and genetic disorders. Yet, our understanding of the quantitative and qualitative mutational impacts of ionizing radiation has been incomplete. On the 14th, Professor Young Seok Ju and his research team from KAIST, in collaboration with Dr. Tae Gen Son from the Dongnam Institute of Radiological and Medical Science, and Professors Kyung Su Kim and Ji Hyun Chang from Seoul National University, unveiled a breakthrough. Their study, led by joint first authors Drs. Jeonghwan Youk, Hyun Woo Kwon, Joonoh Lim, Eunji Kim and Tae-Woo Kim, titled "Quantitative and qualitative mutational impact of ionizing radiation on normal cells," was published in Cell Genomics. Employing meticulous techniques, the research team comprehensively analyzed the whole-genome sequences of cells pre- and post-radiation exposure, pinpointing radiation-induced DNA mutations. Experiments involving cells from different organs of humans and mice exposed to varying radiation doses revealed mutation patterns correlating with exposure levels. (Figure 1) Notably, exposure to 1 Gray (Gy) of radiation resulted in on average 14 mutations in every post-exposure cell. (Figure 2) Unlike other carcinogens, radiation-induced mutations primarily comprised short base deletions and a set of structural variations including inversions, translocations, and various complex genomic rearrangements. (Figure 3) Interestingly, experiments subjecting cells to low radiation dose rate over 100 days demonstrated that mutation quantities, under equivalent total radiation doses, mirrored those of high-dose exposure. "Through this study, we have clearly elucidated the effects of radiation on cells at the molecular level," said Prof. Ju at KAIST. "Now we understand better how radiation changes the DNA of our cells," he added. Dr. Son from the Dongnam Institute of Radiological and Medical Science stated, "Based on this study, we will continue to research the effects of very low and very high doses of radiation on the human body," and further remarked, "We will advance the development of safe and effective radiation therapy techniques." Professors Kim and Chang from Seoul National University College of Medicine expressed their views, saying, "Through this study, we believe we now have a tool to accurately understand the impact of radiation on human DNA," and added, "We hope that many subsequent studies will emerge using the research methodologies employed in this study." This research represents a significant leap forward in radiation studies, made possible through collaborative efforts and interdisciplinary approaches. This pioneering research engaged scholars from diverse backgrounds, spanning from the Genetic Engineering Research Institute at Seoul National University, the Cambridge Stem Cell Institute in the UK, the Institute for Molecular Biotechnology in Austria (IMBA), and the Genome Insight Inc. (a KAIST spin-off start-up). This study was supported by various institutions including the National Research Foundation of Korea, Dongnam Institute of Radiological and Medical Science (supported by Ministry of Science and ICT, the government of South Korea), the Suh Kyungbae Foundation, the Human Frontier Science Program (HFSP), and the Korea University Anam Hospital Korea Foundation for the Advancement of Science and Creativity, the Ministry of Science and ICT, and the National R&D Program.
2024.02.15 View 18303