Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation

• Published in: Journal of radiation research 2015-05, Vol.56 (3), p.493-501
• Main Authors: Matsuu-Matsuyama, Mutsumi, Shichijo, Kazuko, Okaichi, Kumio, Kurashige, Tomomi, Kondo, Hisayoshi, Miura, Shiro, Nakashima, Masahiro
• Format: Article
• Language: English
• Subjects: Adults; Age; Aging - physiology; Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Autophagy - physiology; Autophagy - radiation effects; Biology; Cancer research; Damage; DNA damage; DNA repair; Dose-Response Relationship, Radiation; Gene expression; Genes; Health aspects; Immunohistochemistry; Ionizing radiation; Irradiation; Male; Protein binding; Proteins; Radiation Dosage; Radiation Tolerance - physiology; Radiation, Ionizing; Rats; Rats, Wistar; Risk factors; RNA; Thyroid cancer; Thyroid gland; Thyroid Gland - cytology; Thyroid Gland - physiology; Thyroid Gland - radiation effects; Tumor proteins; Whole-Body Irradiation
• ISSN: 0449-3060; 1349-9157
• DOI: 10.1093/jrr/rrv003

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.