Abstract

Childhood radiation exposure is a known thyroid cancer risk factor. This study evaluated the effects of age on radiation-induced thyroid carcinogenesis in rats irradiated with 8 Gy X-rays. We analyzed cell proliferation, cell death, DNA damage response, and autophagy-related markers in 4-week-old (4W) and 7-month-old (7M) rats and the incidence of thyroid tumors in 4W, 4-month-old (4M), and 7M rats 18 months after irradiation. Cell death and DNA damage response were increased in 4W rats compared to those in controls at 1 month post-irradiation. More Ki-67-positive cells were observed in 4W rats at 12 months post-irradiation. Thyroid tumors were confirmed in 61.9% (13/21), 63.6% (7/11), and 33.3% (2/6) of irradiated 4W, 4M, and 7M rats, respectively, compared to 0%, 14.3% (1/7), and 16.7% (1/6) in the respective nonirradiated controls. There were 29, 9, and 2 tumors in irradiated 4W, 4M, and 7M rats, respectively. The expression of several autophagy components was downregulated in the area surrounding radiation-induced thyroid carcinomas in 4W and 7M rats. LC3 and p62 expression levels decreased in radiation-induced follicular carcinoma in 4W rats. Radiosensitive cells causing thyroid tumors may be more prevalent in young rats, and abrogation of autophagy may be associated with radiation-induced thyroid carcinogenesis.

Details

Title
Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid
Author
Matsuu-Matsuyama Mutsumi 1   VIAFID ORCID Logo  ; Shichijo Kazuko 2 ; Matsuda Katsuya 2 ; Fujimoto Nariaki 3 ; Kondo Hisayoshi 4 ; Miura Shiro 5 ; Kurashige Tomomi 6 ; Nagayama Yuji 6 ; Nakashima Masahiro 7 

1  Nagasaki University, Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki, Japan (GRID:grid.174567.6) (ISNI:0000 0000 8902 2273) 
2  Nagasaki University, Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki, Japan (GRID:grid.174567.6) (ISNI:0000 0000 8902 2273) 
3  Hiroshima University, Department of Disease Model, Research Institute for Radiation Biology and Medicine, Hiroshima, Japan (GRID:grid.257022.0) (ISNI:0000 0000 8711 3200) 
4  Nagasaki University, Biostatistics Section, Atomic Bomb Disease Institute, Nagasaki, Japan (GRID:grid.174567.6) (ISNI:0000 0000 8902 2273) 
5  National Hospital Organization Nagasaki Medical Center, Ōmura, Japan (GRID:grid.415640.2) 
6  Nagasaki University, Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki, Japan (GRID:grid.174567.6) (ISNI:0000 0000 8902 2273) 
7  Nagasaki University, Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki, Japan (GRID:grid.174567.6) (ISNI:0000 0000 8902 2273); Nagasaki University, Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki, Japan (GRID:grid.174567.6) (ISNI:0000 0000 8902 2273) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-021-98481-z
ProQuest document ID
2576737670
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.