Morphological and functional changes in neonatally X-irradiated thyroid gland in rats

Abstract

Exposure to ionized radiation in childhood has been recognized as a risk factor for the development of thyroid cancer and possibly for other thyroid disorders. However, the effects of neonatal radiation exposure on thyroid morphology and functions have never been explored despite its potential importance. One-week-old male Wistar rats were subjected to cervical X-irradiation at 6 and 12 Gy. Animals were examined at the ages of 2, 8 and 18 weeks old. For comparison, 8-weekold rats were cervically X-irradiated at the same doses. Thyroid histology was examined by computer-assisted microscopy to measure areas of colloid and epithelium of thyroid follicles as well as epithelial heights. In rats that received cervical Xirradiation at 1 week old, the colloid size of thyroid follicles decreased at the age of 8 weeks old in a radiation-dose dependent manner. This morphological change was persistently found at 18 weeks old. There were no significant differences in serum total T3 or T4 levels among the groups. Serum TSH levels increased significantly in 8-week-old rats neonatally X-irradiated. Thyroglobulin (Tg) mRNA and protein expressions were significantly decreased in the neonatally-irradiated group while thyroid peroxidase mRNA express increased at 18 weeks old. None of these changes were observed in the rats X-irradiated at 8 weeks old. In conclusion, our results clearly demonstrated that neonatal rat thyroid was sensitive to ionized radiation, developing specific morphological changes characterized by smaller thyroid follicles along with changes in serum TSH levels and Tg expressions in the thyroid tissue. AN ASSOCIATION between childhood radiation and an increased risk of thyroid cancer has been well established. Early investigations of neoplasms in those who were treated with X-rays in infancy suggested that radiation exposure in childhood increases the risk of thyroid cancer [1]. A study in rats exposed to cervical Xirradiation showed that neonatal rats were more susceptible to developing thyroid cancer than adult animals [2]. Moreover, the rapid increase in childhood thyroid cancer after the Chernobyl nuclear plant accident clearly demonstrated the risk of radiation exposure in childhood and adolescence [3,4]. A cohort study of Japanese atomic bomb survivors also showed an excess thyroid cancer risk associated with childhood radiation exposure [5]. It has been suggested that a high mitotic rate of thyroid fol-

Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid

“…Serum TSH levels were significantly increased in irradiated neonatal rats. It has been suggested that epithelial height is inversely related to serum TSH levels 7 . However, in this study, the serum TSH level was only slightly increased in 4W rats compared to that in the control at 6 months post-irradiation, and this change was not significant.…”

“…The five largest thyroid follicles from each field of view were selected for measurement. The epithelial height and colloid area were measured using the BZ-II Analyzer software (Keyence Co.) as described previously 7 . The first and second layers of follicles from the outside were defined as the peripheral zone, while the other area was defined as the central zone 34 .…”

“…Lee et al reported that the incidence of thyroid carcinoma increased with dose in 6-week-old female rats irradiated with X-rays up to 1060 rad 6 . Moreover, the thyroids of neonatal rats (1-week-old) are more sensitive to ionizing radiation at 12 Gy compared to those from adult rats, as evidenced by body weight loss and decreased colloid size in thyroid follicles 7 . However, few studies have experimentally investigated radiation-induced thyroid carcinogenesis and age effect.…”

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

“…However, laboratory investigations with animal models have rarely been conducted to understand the underlying mechanisms. We recently demonstrated that the thyroid in rats X-irradiated at the age of 5–6 days developed the specific morphological changes characterized by smaller-sized follicles 15 . In the present study, we further investigated this model to understand the impacts of neonatal irradiation on the thyroid.…”

“…However, studies to investigate the underlying mechanisms in animal models have rarely been performed 14 . Previously, we cervically X-irradiated 5–6 days old Wistar rats and, after comparing them with rats irradiated at 8 weeks old, found that thyroid follicle sizes were reduced only after the neonatal irradiation 15 . In the present study, we further investigated this animal model by examining the effects at different radiation doses and ages.…”