Matsuda Katsuya, Kurohama Hirokazu, Kuwatsuka Yutaka, Iwanaga Akira, Murota Hiroyuki, Nakashima Masahiro
Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
J Radiat Res. 2024 Dec 16;65(Supplement_1):i57-i66. doi: 10.1093/jrr/rrae035.
We previously reported endogenous activation of the DNA damage response (DDR) in the epidermis surrounding basal cell carcinoma resected from Nagasaki atomic bomb survivors, suggesting the presence of genomic instability (GIN) in the survivors as a late effect of radiation. Dual-color immunofluorescence (IF) analysis of TP53-binding protein-1 (53BP1) and a proliferative indicator, Ki-67, to elucidate GIN in tumor tissues revealed that abnormal 53BP1 expression is closely associated with carcinogenesis in several organs. The present study aimed to confirm the presence of radiation-induced GIN in the non-neoplastic epidermis of patients with radiation-induced skin cancer. Formalin-fixed paraffin-embedded tissues were obtained from all participants between 2008 and 2019 at the Nagasaki University Hospital. 53BP1 nuclear expression was examined using dual-color IF analysis with Ki-67 expression to assess the extent and integrity of the DDR. Expressions of gamma-H2AX, p53 and p21 were also analyzed using the dual-color IF analysis for their association with 53BP1. The results of this study provide evidence for sporadic activation of the DDR in medically irradiated and ultraviolet-exposed epidermis as a long-lasting radiation effect, which is a predisposition to skin cancer. Furthermore, the incidence of abnormal 53BP1 expression in cancer cells was higher than in non-neoplastic epidermal cells surrounding cancer, suggesting a correlation between the type of 53BP1 and the malignant potential of skin tumors. This study highlights the usefulness of dual-color IF for 53BP1 (and Ki-67) as an indicator to estimate the level of GIN as a long-lasting health effect of radiation exposure.
我们之前报道了从长崎原子弹爆炸幸存者身上切除的基底细胞癌周围表皮中DNA损伤反应（DDR）的内源性激活，这表明幸存者存在基因组不稳定性（GIN），这是辐射的晚期效应。通过对TP53结合蛋白1（53BP1）和增殖指标Ki-67进行双色免疫荧光（IF）分析，以阐明肿瘤组织中的GIN，结果显示异常的53BP1表达与多个器官的致癌作用密切相关。本研究旨在证实辐射诱发的皮肤癌患者的非肿瘤性表皮中存在辐射诱导的GIN。2008年至2019年间，从长崎大学医院的所有参与者身上获取了福尔马林固定石蜡包埋组织。使用与Ki-67表达的双色IF分析来检测53BP1的核表达，以评估DDR的程度和完整性。还使用双色IF分析来分析γ-H2AX、p53和p21的表达与53BP1的相关性。本研究结果为DDR在医学照射和紫外线暴露的表皮中作为一种持久的辐射效应而散在激活提供了证据，这种效应是皮肤癌的易患因素。此外，癌细胞中53BP1异常表达的发生率高于癌周围的非肿瘤性表皮细胞，这表明53BP1的类型与皮肤肿瘤的恶性潜能之间存在相关性。本研究强调了将53BP1（和Ki-67）的双色IF作为评估GIN水平的指标的有用性，GIN是辐射暴露的一种持久健康效应。
