Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?
Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?
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DOI：
10.3109/09553002.2010.522686
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发表时间：
2011-02-01
影响因子：
2.6
通讯作者：
Baulch, Janet E.
中科院分区：
文献类型：
--
作者：
Aypar, Umut;Morgan, William F.;Baulch, Janet E.
结论：除了广泛研究的辐射靶向效应外，现在很明显，非靶向延迟效应（如RIGI）也是重要的辐射后结果。在RIGI中，未照射的子代细胞在亲本细胞照射后的延迟时间显示表型变化。RIGI被认为在致癌过程中很重要;然而，其发生的机制仍有待阐明。在Morgan及其同事开发的基因组不稳定的克隆中，辐射诱导的突变，双链断裂或信使RNA（mRNA）水平的变化不能单独解释RIGI的启动或延续。由于DNA序列的改变不能完全解释RIGI的机制，因此可能涉及遗传性表观遗传改变。已知表观遗传学在许多细胞过程中起重要作用，表观遗传学畸变可导致癌变。近年来放射生物学领域的研究表明，甲基化模式的改变可能参与了RIGI。这些线索使我们假设表观遗传学可能是理解RIGI背后机制的缺失环节。
Conclusion: aEuro integral In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis; however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in messenger RNA (mRNA) levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesise that epigenetics may be the missing link in understanding the mechanism behind RIGI.