Single neonatal irradiation induces long-term gene expression changes in the thyroid gland, which may be involved in the tumorigenesis

• Published in: Scientific reports 2021-12, Vol.11 (1), p.23620-23620, Article 23620
• Main Authors: Fujimoto, Nariaki, Matsuu-Matsuyama, Mutsumi, Nakashima, Masahiro
• Format: Article
• Language: English
• Subjects: 631/67/1459; 631/67/1857; 631/67/2332; 692/163; 692/420/755; Adenoma; Animal models; Animals; Apoptosis; Body Weight; Carcinogenesis; Cervix; Children; Combined treatment; Follicles; Gene expression; Gene Expression - radiation effects; Humanities and Social Sciences; Humans; Infant, Newborn; Iodine; Ionizing radiation; Irradiation; multidisciplinary; Neonates; Nutrient deficiency; Organ Size - radiation effects; Radiation; Rats; Rats, Wistar; Risk factors; Science; Science (multidisciplinary); Thyroid; Thyroid cancer; Thyroid gland; Thyroid Gland - metabolism; Thyroid Hormones - blood; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Tumorigenesis; Tumors; X-rays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-03012-5

Exposure to ionizing radiation in childhood has been recognized as a risk factor for thyroid cancer. We previously demonstrated that neonatal X-irradiation induced specific deformation of the thyroid follicles. Here, we further analyzed this model to understand the possible relationship with thyroid carcinogenesis. Wistar rats were subjected to cervical X-irradiation at different ages of 1–8 weeks old and at different doses of 1.5–12 Gy. For tumor promotion, rats were fed with an iodine-deficient diet (IDD). In cervically X-irradiated neonatal rats, the size of thyroid follicles decreased, accompanied by an increase in the number of TUNEL-positive cells. Fas and Lgals3 mRNA levels increased, while Mct8 and Lat4 expressions decreased. The co-administration of IDD induced the proliferation and the upregulation in Lgals3 expression, resulting in thyroid adenoma development at 28 weeks post-exposure. Our data demonstrated that single neonatal X-irradiation induced continuous apoptotic activity in the thyroid with the long-term alternation in Fas , Mct8 , Lat4 , and Lgals3 mRNA expressions. Some of these changes were similar to those induced by IDD, suggesting that neonatal X-irradiation may partially act as a thyroid tumor promoter. These radiation-induced thyroidal changes may be enhanced by the combined treatment with IDD, resulting in the early development of thyroid adenoma.