Fax: (011) 81-95-849-7130
Genomic instability in the epidermis induced by atomic bomb (A-bomb) radiation
A long-lasting health effect in A-bomb survivors
Article first published online: 10 JUN 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 16, pages 3782–3790, 15 August 2009
How to Cite
Naruke, Y., Nakashima, M., Suzuki, K., Kondo, H., Hayashi, T., Soda, M. and Sekine, I. (2009), Genomic instability in the epidermis induced by atomic bomb (A-bomb) radiation. Cancer, 115: 3782–3790. doi: 10.1002/cncr.24405
- Issue published online: 3 AUG 2009
- Article first published online: 10 JUN 2009
- Manuscript Accepted: 9 JAN 2009
- Manuscript Revised: 6 JAN 2009
- Manuscript Received: 21 AUG 2008
- Nagasaki University Global Center of Excellence Program
- Scientific Research from the Japanese Ministry of Education, Science, Sports, and Culture. Grant Number: 20590367
- Research Project of Atomic Bomb Diseases from the Japanese Ministry of Health, Labor, and Welfare
- atomic bomb;
- genomic instability;
- p53 binding protein 1;
- basal cell carcinoma
Radiation etiology is suggested in the occurrence of basal cell carcinoma (BCC) of the skin among atomic bomb (A-bomb) survivors. Any genotoxicity, including ionizing radiation, can induce a DNA damage response (DDR), leading to genomic instability (GIN), which allows the accumulation of mutations during tumorigenesis. In this study, the authors evaluated the presence of GIN in the epidermis of survivors as a late effect of A-bomb radiation.
In total, 146 BCCs, including 23 cases arising from nonexposed skin, were identified in survivors from 1968 to 1999. The incidence rate (IR) of BCC was calculated with stratification by distance in kilometers from the hypocenter (≤1.5 km, 1.6-2.9 km, and ≥3 km). Nineteen epidermal samples surrounding BCC at the nonexposed sites were collected and tested for p53 binding protein 1 (53BP1) expression with immunofluorescence. 53BP1 rapidly forms nuclear foci at the sites of DNA double strand breaks (DSBs). Because 1 manifestation of GIN is the induction of endogenous DSBs, the level of 53BP1-focus formation (DDR type) can be considered as a marker for GIN.
The incidence rate of BCC increased significantly as exposure distance approached the hypocenter. Of the 7 epidermal samples from the proximal group (≤1.5 km), 5 samples predominantly expressed DDR and an abnormal type of 53BP1 expression. In contrast, 4 of 5 samples from the distal group (≥3 km) and all samples from the control group predominantly expressed the stable type of 53BP1 expression in the epidermis.
The current results demonstrated the endogenous activation of DDR in the epidermis surrounding BCC in the proximal group, suggesting the presence of a GIN in the survivors as a late effect of A-bomb radiation, which may indicate a predisposition to cancer. Cancer 2009. © 2009 American Cancer Society.