Unit of Cellular Networks and Molecular Therapeutic Targets, Department of Research and Advanced Technologies, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), c/o Sapienza University, 00185 Rome, Italy.
Int J Mol Sci. 2024 Jun 27;25(13):7064. doi: 10.3390/ijms25137064.
Recurrent computed tomography (CT) examination has become a common diagnostic procedure for several diseases and injuries. Though each singular CT scan exposes individuals at low doses of low linear energy transfer (LET) radiation, the cumulative dose received from recurrent CT scans poses an increasing concern for potential health risks. Here, we evaluated the biological effects of recurrent CT scans on the DNA damage response (DDR) in human fibroblasts and retinal pigment epithelial cells maintained in culture for five months and subjected to four CT scans, one every four weeks. DDR kinetics and eventual accumulation of persistent-radiation-induced foci (P-RIF) were assessed by combined immunofluorescence for γH2AX and 53BP1, i.e., γH2AX/53BP1 foci. We found that CT scan repetitions significantly increased both the number and size of γH2AX/53BP1 foci. In particular, after the third CT scan, we observed the appearance of giant foci that might result from the overlapping of individual small foci and that do not associate with irreversible growth arrest, as shown by DNA replication in the foci-carrying cells. Whether these giant foci represent coalescence of unrepaired DNA damage as reported following single exposition to high doses of high LET radiation is still unclear. However, morphologically, these giant foci resemble the recently described compartmentalization of damaged DNA that should facilitate the repair of DNA double-strand breaks but also increase the risk of chromosomal translocations. Overall, these results indicate that for a correct evaluation of the damage following recurrent CT examinations, it is necessary to consider the size and composition of the foci in addition to their number.
反复进行计算机断层扫描（CT）检查已成为多种疾病和损伤的常用诊断程序。虽然每次单独的 CT 扫描都会使个体受到低线性能量转移（LET）辐射的低剂量暴露，但反复进行 CT 扫描所接受的累积剂量对潜在健康风险的担忧却在不断增加。在这里，我们评估了反复 CT 扫描对培养了五个月的人成纤维细胞和视网膜色素上皮细胞中 DNA 损伤反应（DDR）的生物学影响，这些细胞在四个 CT 扫描中，每四个星期进行一次扫描。通过对 γH2AX 和 53BP1 进行联合免疫荧光染色，评估 DDR 动力学和持久性辐射诱导焦点（P-RIF）的最终积累，即γH2AX/53BP1 焦点。我们发现 CT 扫描重复次数显著增加了 γH2AX/53BP1 焦点的数量和大小。特别是在第三次 CT 扫描后，我们观察到了巨型焦点的出现，这些焦点可能是由于单个小焦点的重叠而形成的，并且不会导致不可逆的生长停滞，因为焦点携带细胞中的 DNA 复制表明了这一点。这些巨型焦点是否代表了与单次高 LET 辐射暴露后报告的未修复 DNA 损伤的融合仍然不清楚。然而，从形态上看，这些巨型焦点类似于最近描述的受损 DNA 的分隔化，这应该有助于修复 DNA 双链断裂，但也会增加染色体易位的风险。总的来说，这些结果表明，为了正确评估反复 CT 检查后的损伤，除了焦点的数量外，还需要考虑焦点的大小和组成。
