Genomic instability in the epidermis induced by atomic bomb (A-bomb) radiation: a long-lasting health effect in A-bomb survivors.
BACKGROUND
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.


METHODS
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 (< or =1.5 km, 1.6-2.9 km, and > or =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.


RESULTS
: The incidence rate of BCC increased significantly as exposure distance approached the hypocenter. Of the 7 epidermal samples from the proximal group (< or =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 (> or =3 km) and all samples from the control group predominantly expressed the stable type of 53BP1 expression in the epidermis.


CONCLUSIONS
: 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.
Naruke
Yuki
Y
Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Nakashima
Masahiro
M
Suzuki
Keiji
K
Kondo
Hisayoshi
H
Hayashi
Tomayoshi
T
Soda
Midori
M
Sekine
Ichiro
I
D000368:Aged; D051017:Apoptosis Regulatory Proteins; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D004249:DNA Damage; D004817:Epidermis / Q000528:radiation effects*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000235:genetics*; D054043:Nuclear Weapons; D012737:Sex Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017741:Survivors
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C090468:TP53BP2 protein, human