Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation.
Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation.
复制标题
年龄对大鼠甲状腺对电离辐射的敏感性的影响。
DOI：
10.1093/jrr/rrv003
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发表时间：
2015-05
影响因子：
2
通讯作者：
Nakashima M
中科院分区：
文献类型：
--
作者：
Matsuu-Matsuyama M;Shichijo K;Okaichi K;Kurashige T;Kondo H;Miura S;Nakashima M
儿童时期暴露于电离辐射是众所周知的甲状腺癌风险因素。我们的研究评估了年龄对大鼠甲状腺放射敏感性的影响。将4周龄（4 W）、7周龄（7 W）和8月龄（8 M）雄性Wistar大鼠暴露于8戈伊全身X射线照射。照射后3-72 h取出甲状腺，未照射的甲状腺作为对照。通过免疫组织化学评价Ki 67阳性和p53结合蛋白1（53 BP 1）病灶形成（DNA损伤反应）。通过蛋白质印迹法测定参与DNA损伤反应（p53、p53在丝氨酸15处磷酸化、p21）、凋亡（切割的半胱天冬酶-3）和自噬（LC 3、p62）的蛋白质的量。使用聚合酶链反应阵列定量84个关键自噬相关基因的mRNA水平。4 W（高增殖活性）和7 W甲状腺组织中Ki 67阳性细胞数量在照射后明显减少。53 BP 1灶的数量和p53在丝氨酸15磷酸化的量在照射后3小时增加，与年龄无关。在任何年龄组均未检测到细胞凋亡或p53、p21或裂解的caspase-3水平的增加。LC 3-II和p62的水平增加照射4 W，但不是8 M甲状腺，而几个自噬相关基因的表达是在4 W高于8 M照射甲状腺。照射增加了编码促凋亡蛋白的基因在4 W和8 M甲状腺的表达。总之，尽管在未成熟和成年甲状腺中表达了一些促凋亡基因，但未观察到细胞凋亡或p53积聚。辐射诱导自噬在未成熟的，但不是在成年，大鼠甲状腺。
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.
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DOI：
10.1006/bbrc.1994.1412
发表时间：
1994-04-15
影响因子：
3.1
作者：
DREMIER, S;GOLSTEIN, J;ROBAYE, B
通讯作者：
ROBAYE, B
影响因子：
6.4
作者：
Nakashima, Masahiro;Suzuki, Keiji;Sekine, Ichiro
通讯作者：
Sekine, Ichiro
影响因子：
21.3
作者：
Tooze, Sharon A.;Yoshimori, Tamotsu
通讯作者：
Yoshimori, Tamotsu
影响因子：
56.9
作者：
Yu, L;Alva, A;Lenardo, MJ
通讯作者：
Lenardo, MJ
影响因子：
6
作者：
Koike, Masato;Shibata, Masahiro;Uchiyama, Yasuo
通讯作者：
Uchiyama, Yasuo