title: Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation.
abstract: Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3-72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids.
authors.affiliation: Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan mutsumi@nagasaki-u.ac.jp.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Matsuu-Matsuyama
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shichijo
authors.affiliation: Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Kumio
authors.initials: K
authors.lastname: Okaichi
authors.affiliation: Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kurashige
authors.affiliation: Biostatistics Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Miura
authors.affiliation: Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D008297:Male; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology*; D011839:Radiation, Ionizing; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D014916:Whole-Body Irradiation
chemical_list: D051017:Apoptosis Regulatory Proteins
keywords: X-ray; apoptosis; autophagy; p53 binding protein 1; rat; thyroid