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

Childhood radiation exposure is a known thyroid cancer risk factor. This study evaluated the effects of age on radiation-induced thyroid carcinogenesis in rats irradiated with 8 Gy X-rays. We analyzed cell proliferation, cell death, DNA damage response, and autophagy-related markers in 4-week-old (4W) and 7-month-old (7M) rats and the incidence of thyroid tumors in 4W, 4-month-old (4M), and 7M rats 18 months after irradiation. Cell death and DNA damage response were increased in 4W rats compared to those in controls at 1 month post-irradiation. More Ki-67-positive cells were observed in 4W rats at 12 months post-irradiation. Thyroid tumors were confirmed in 61.9% (13/21), 63.6% (7/11), and 33.3% (2/6) of irradiated 4W, 4M, and 7M rats, respectively, compared to 0%, 14.3% (1/7), and 16.7% (1/6) in the respective nonirradiated controls. There were 29, 9, and 2 tumors in irradiated 4W, 4M, and 7M rats, respectively. The expression of several autophagy components was downregulated in the area surrounding radiation-induced thyroid carcinomas in 4W and 7M rats. LC3 and p62 expression levels decreased in radiation-induced follicular carcinoma in 4W rats. Radiosensitive cells causing thyroid tumors may be more prevalent in young rats, and abrogation of autophagy may be associated with radiation-induced thyroid carcinogenesis

Internal radiation exposure from 137Cs and its association with the dietary habits of residents from areas affected by the Chernobyl nuclear accident, Ukraine: 2016-2018.

The total annual effective dose has steadily decreased since the fallout of the Chernobyl Nuclear Power Plant. However, chronic internal exposure to 137Cs still persists and fluctuates in a complex and unpredictable manner. Recently, body contamination was found to primarily occur owing to the intake of forest foodstuffs that contain long-lived 137Cs. Forest foodstuffs may have up to 100 times higher concentration of cesium than does local milk and meat. The present study aimed to investigate the recent dietary habits of residents in the Zhytomyr region of Ukraine, and assess the effect of the intake of forest foodstuffs on the increase in internal radioactivity from 137Cs. We screened 1,612 participants, from July 2016 to February 2018 for internal radioactivity, using whole-body counter at Korosten Medical Center and surveyed their background and intake habits. We analyzed the association among food type, intake frequency, and internal exposure dose. The analysis revealed that nearly 90% of the participants regularly consumed one of the forest foodstuffs (mushrooms, berries, fish) or milk. Nearly 80% of the participants indicated that they consumed mushrooms or berries or both. Internal radioactivity was detected in 30% of the participants. The diet that included mushrooms exhibited the highest internal radioactivity. The lowest Bq/kg concentration was observed in the only-berry group, following the no-intake group. There was a significant correlation between the intake frequency and the magnitude of Bq/kg. Radioactivity detected in the mushroom-berry and only-mushroom group were 8.6 and 9.2 Bq/kg, respectively. The lowest and highest intake frequency showed a radioactivity of 2.4 and 7.5 Bq/kg, respectively. Radioactivity in the winter season was significantly higher than that in other seasons. In conclusion, our study revealed that internal radioactivity varies depending on the type of food, intake frequency, and season

Norepinephrine Enhances Radiosensitivity in Rat Ileal Epithelial Cells

We previously reported that the apoptosis index in jejunal crypt cells after X irradiation was greater in spontaneously hypertensive rats than in Wistar-Kyoto rats. Moreover, these same cells showed a suppression of apoptosis when reserpine was administered to induce sympathetic dysfunction in spontaneously hypertensive rats or Wistar-Kyoto rats.1) Whether the hyperfunction of the sympathetic nervous system is involved in the high susceptibility of the jejunal crypt cells to radiation-induced apoptosis was the subject of this study. The effect of norepinephrine (NE) on cell survival was examined using the colony formation assay after X-ray irradiation of rat ileal epithelial cells (IEC-18). The addition of 1 μM NE decreased the surviving fraction of cells irradiated with 6 Gy from 37% to 8%. The radiosensitivity of IEC-18 cells was enhanced by the addition of 1 μM of NE. The irradiation and treatment with NE also resulted in an increased cellular apoptotic rate. These results showing enhanced radiosensitivity of rat ileal epithelial cells by NE suggest that NE may be one of the factors which aggravate acute radiation injury in the intestine

The Protective Effect of Interleukin-11 on the Cell Death Induced by X-ray Irradiation in Cultured Intestinal Epithelial Cell

Interleukin-11/PI3K/X-ray Irradiation/Intestinal Epithelial Cell. Interleukin-11 (IL-11) is a well known anti-inflammatory cytokine that is associated with cell growth, and also participates in limiting X-ray irradiation induced intestinal mucosal injury. The aim of this study was to evaluate the protective effect of IL-11 on the cell injury induced by X-ray irradiation in rat intestinal epithelial IEC-18 cells. Recombinant human IL-11 (rhIL-11) treated cells were irradiated and then examined for cell viability. To evaluate irradiation injury, trypan blue staining was used to detect the dead cells. The viability of irradiated cells was up-regulated by rhIL-11 treatment and also resulted in the activation of p90 ribosomal S6 kinase (p90RSK) and S6 ribosomal protein (S6Rp). Wortmannin, a specific inhibitor of PI3K, suppressed the activation of S6Rp in rhIL-11 treated cells, and decreased the up-regulation of viability by rhIL-11 treatment in irradiated cells. The TUNEL assay was also perfomed to estimate the rate of apoptosis in X-ray induced cell death. There was no difference in the results between trypan blue staining and the TUNEL assay. Further, rhIL-11 down-regulated the expression of cleaved caspase-3 in irradiated cells. These results suggest that rhIL-11 may play an important role in protection from radiation injury

Protective effects of a cystine and theanine mixture against acute radiation injury in rats

This study aims to examine the effects of cystine and theanine (CT), which increases glutathione biosynthesis, on the survival rate and acute radiation injury of the small intestine and bone marrow using a rat model. CT pre-treatment (280 mg/kg for 5 days) significantly improved weight loss and survival rate of rats as compared with the control group after 5 Gy. CT pre-treatment significantly increased the rate of mucosa and crypt length, and decreased the number of apoptotic cells, TUNEL and cleaved caspase-3 positive cells, while increasing the number of mitotic cells and Ki-67 positive cells in jejunal crypts and villi compared to control rats post-irradiation. CT also suppressed bone marrow cell loss and reduced the number of apoptotic cells in bone marrow. These results suggest a protective effect of CT pre-treatment for acute injury after irradiation through apoptosis inhibition and increased proliferative activity in jejunal crypt cells and bone marrow cells

Protection by Polaprezinc Against Radiation-Induced Apoptosis in Rat Jejunal Crypt Cells

Polaprezinc, an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. Polaprezinc has been shown to prevent gastric mucosal injury. The anti ulcer effects of polaprezinc have been ascribed to its antioxidative property. The effect of polaprezinc on ionizing radiation-induced apoptosis was studied in the jejunal epithelial crypt cells of rats. Seven-to eight week-old Wistar rats, which were treated with 100 mg/kg of polaprezinc orally 1h before irradiation or 2% carboxymethyl cellulose sodium in controls, were exposed to whole body X-ray irradiation at 2 Gy. The number of apoptotic cells per jejunum crypt was counted in haematoxylin and eosin stained sections at 0-6 h after irradiation. TUNEL positive cells and immunopositive cells for active caspase-3 per crypt were also counted. Accumulation of p53, p21^ and Bax expression in the jejunum after irradiation were examined by Western blot analyses. Polaprezinc treatment given prior to radiation resulted in a significant reduction in numbers of apoptotic cells, TUNEL positive cells and active caspase-3 immunopositive cells in jejunal crypt cells. Polaprezinc treatment resulted in decreases of p53 accumulation, p21^ and Bax expression after irradiation. Polaprezinc has a protective effect against ionizing radiation induced apoptosis in rat jejunal crypt cells