Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Radiat Res. 2011 May;175(5):575-87. doi: 10.1667/RR2390.1. Epub 2011 Mar 4.
It has been acknowledged for many years that radiation exposure induces delayed, non-targeted effects in the progeny of the irradiated cell. Evidence is beginning to demonstrate that among these delayed effects of radiation are epigenetic aberrations, including altered DNA methylation. To test the hypothesis that differences in radiation quality affect radiation-induced DNA methylation profiles, normal AG01522 and RKO colon carcinoma cells were exposed to low-LET X rays and protons or high-LET iron ions. DNA methylation was then evaluated at delayed times using assays for p16 and MGMT promoter, LINE-1 and alu repeat element, and global methylation. The results of these experiments demonstrated radiation-induced changes in repeat element and global DNA methylation patterns at ∼20 population doublings postirradiation. Further, radiation-induced changes in repeat element and global DNA methylation were more similar between proton- and iron-ion-irradiated cells than X-irradiated cells, suggesting that radiation quality rather than LET alone affects the radiation-induced epigenetic profile. Since alterations in DNA methylation have also emerged as one of the most consistent molecular alterations in cancer, these data also suggest the possibility that radiation-induced carcinogenic risk might be affected by radiation quality.
多年来，人们已经认识到辐射暴露会在被照射细胞的后代中引起延迟的、非靶向的效应。有证据开始表明，在这些辐射的延迟效应中包括表观遗传异常，包括改变 DNA 甲基化。为了验证辐射质量差异是否会影响辐射诱导的 DNA 甲基化谱的假设，用低 LET X 射线和质子或高 LET 铁离子照射正常的 AG01522 和 RKO 结肠癌细胞。然后在辐射后约 20 个细胞倍增时，使用 p16 和 MGMT 启动子、LINE-1 和 alu 重复元件和全基因组甲基化的测定来评估 DNA 甲基化。这些实验的结果表明，在辐射后，重复元件和全基因组 DNA 甲基化模式发生了辐射诱导的变化。此外，与 X 射线照射的细胞相比，质子和铁离子照射的细胞中重复元件和全基因组 DNA 甲基化的辐射诱导变化更为相似，这表明辐射质量而不仅仅是 LET 影响辐射诱导的表观遗传谱。由于 DNA 甲基化的改变也已成为癌症中最一致的分子改变之一，这些数据还表明，辐射诱导的致癌风险可能受到辐射质量的影响。
