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Radiation-induced DNA damage and delayed induced genomic instability

Abstract

Ionizing radiation induces genomic instability, which is transmitted over many generations after irradiation through the progeny of surviving cells. Induced genomic instability is manifested as the expression of the following delayed effects: delayed reproductive death or lethal mutation, chromosomal instability, and mutagenesis. Since induced genomic instability accumulates gene mutations (actually genomic instability is the process whereby gene mutation increases subtle difference) and gross chromosomal rearrangements, it has been thought to play a role in radiation-induced carcinogenesis. Radiation-induced genomic instability exerts its effects for prolonged periods of time, suggesting the presence of a mechanism by which the initial DNA damage in the surviving cells is memorized. Recent studies have shown that such memory transmission causes delayed DNA breakage, which in turn plays a role in the induction of delayed phenotypes. Although radiation-induced genomic instability has been studied for years, many questions remain to be answered. This review summarizes the current data on radiation-induced genomic instability. In particular, the mechanism(s) involved in the initiation and perpetuation of radiation-induced genomic instability, and a role of delayed activation of p53 protein are discussed.

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Acknowledgements

This work was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. We thank Dr John B Little and Dr William F Morgan for their critical reading of the manuscript and useful comments. We also gratefully acknowledge the many students, past and present.

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Correspondence to Keiji Suzuki.

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Suzuki, K., Ojima, M., Kodama, S. et al. Radiation-induced DNA damage and delayed induced genomic instability. Oncogene 22, 6988–6993 (2003). https://doi.org/10.1038/sj.onc.1206881

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