Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson, Houston, TX, 77030, USA.
Sci Rep. 2022 Feb 8;12(1):2107. doi: 10.1038/s41598-022-06071-4.
I is used clinically for therapy, and may be released during nuclear accidents. After the Chernobyl accident papillary thyroid carcinoma incidence increased in children, but not adults. The aims of this study were to compare I irradiation-dependent differences in RNA and protein expression in the thyroid and plasma of young and adult rats, and identify potential age-dependent biomarkers for I exposure. Twelve young (5 weeks) and twelve adult Sprague Dawley rats (17 weeks) were i.v. injected with 50 kBq I (absorbed dose to thyroid = 0.1 Gy), and sixteen unexposed age-matched rats were used as controls. The rats were killed 3-9 months after administration. Microarray analysis was performed using RNA from thyroid samples, while LC-MS/MS analysis was performed on proteins extracted from thyroid tissue and plasma. Canonical pathways, biological functions and upstream regulators were analysed for the identified transcripts and proteins. Distinct age-dependent differences in gene and protein expression were observed. Novel biomarkers for thyroid I exposure were identified: (PTH), age-dependent dose response (CA1, FTL1, PVALB (youngsters) and HSPB6 (adults)), thyroid function (Vegfb (adults)). Further validation using clinical samples are needed to explore the role of the identified biomarkers.
I 用于临床治疗,并且可能在核事故中释放。切尔诺贝利事故后,儿童甲状腺癌的发病率增加,但成年人没有。本研究的目的是比较 I 照射对年轻和成年大鼠甲状腺和血浆中 RNA 和蛋白质表达的影响,并鉴定潜在的与年龄相关的 I 暴露生物标志物。12 只年轻(5 周)和 12 只成年 Sprague Dawley 大鼠(17 周)经静脉注射 50kBq I(甲状腺吸收剂量=0.1Gy),16 只未暴露的同龄大鼠作为对照。大鼠在给药后 3-9 个月处死。使用甲状腺样本中的 RNA 进行微阵列分析,同时使用从甲状腺组织和血浆中提取的蛋白质进行 LC-MS/MS 分析。对鉴定出的转录物和蛋白质进行了经典途径、生物学功能和上游调控因子分析。观察到基因和蛋白质表达存在明显的年龄依赖性差异。鉴定出甲状腺 I 暴露的新型生物标志物:(PTH)、年龄依赖性剂量反应(CA1、FTL1、PVALB(年轻人)和 HSPB6(成年人))、甲状腺功能(Vegfb(成年人))。需要使用临床样本进一步验证,以探讨所鉴定生物标志物的作用。