Effect of hydroxychloroquine pre-treatment on acute radiosensitivity of thyroid in young rats

This study aimed to determine the effects of hydroxychloroquine [HCQ]-induced autophagy suppression prior to irradiation on radiosensitivity of the thyroid gland and compared it with that observed in the liver. Briefly, 6-week-old Wistar rats were divided into non-treated (saline) and treated groups (HCQ 200 mg/kg administered thrice orally). The treated group was further divided into irradiated (4 Gy of whole-body X-ray) and non-irradiated (NR) groups. The liver and thyroid tissues were resected from the NR and irradiated (at 3, 6 and 24 h) group rats. Changes in apoptosis (number of TUNEL-positive cells), proliferation (number or rate of Ki-67-positive cells), DNA damage response (number of 53BP1 nuclear foci and phospho-p53Ser15 expression), and autophagy-related molecules (LC3 and p62 expression and autophagy-related gene expression) in the liver and thyroid were examined. More TUNEL-positive cells were present in the liver of HCQ-treated group than in that of non-treated group at each time point, but no changes in thyroid were observed between groups at any time point. Fewer Ki-67-positive cells were observed in the liver and thyroid of HCQ-treated group than in non-treated group after irradiation. The number of 53BP1 nuclear foci in the thyroid increased slightly in the HCQ-treated group at 3 h compared with that in non-treated and NR group. Increased p62 expression was observed at 3 and 6 h in the liver, but not in the thyroid, in HCQ-treated group. The punctate staining for LC3 and p62 in the thyroid cytoplasm of HCQ-treated rats was observed in NR and irradiation groups. A lower expression of five autophagy machinery component genes and 12 autophagy regulatory genes was observed in the HCQ-treated irradiated rats than in non-treated irradiated rats at 24 h. HCQ administration before irradiation reduced cell proliferation in the thyroid gland with a slight increase in DNA damage response and decrease in autophagy-related gene expression. However, no change was observed in apoptosis, unlike in the liver. In the liver, radiation exposure after HCQ administration induced apoptosis, eliminating the damaged cells. In contrast, in the thyroid, damaged cells might continue to survive as they are not eliminated by apoptosis.