The circadian clock protects against acute radiation-induced dermatitis.
The circadian clock protects against acute radiation-induced dermatitis.
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DOI：
10.1016/j.taap.2020.115040
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发表时间：
2020-07-15
影响因子：
3.8
通讯作者：
Gaddameedhi S
中科院分区：
文献类型：
--
作者：
Dakup PP;Porter KI;Gaddameedhi S
放射性皮炎是接受放射治疗（RT）的癌症患者中常见的疾病，是由电离辐射（IR）诱导皮肤细胞DNA链断裂引起的。RT在癌症治疗中的广泛使用使得最小化RT诱导的毒性（包括放射性皮炎）变得重要。这项研究试图确定生物钟是否在减少放射性皮炎中起保护作用。我们用6戈伊的IR全身照射对照（日班）、环境干扰（轮换）和遗传干扰（每1/2−/−）昼夜节律条件下的小鼠。与对照小鼠相比，生物钟中断小鼠的放射性皮炎斑点数量显著增加。此外，昼夜节律钟被破坏的小鼠表现出Bmal 1蛋白水平降低，这是一种使昼夜节律同步的角质形成细胞对IR诱导的DNA损伤敏感的现象。此外，与对照小鼠相比，皮肤表型结果与体重显著降低和血液细胞中基因组DNA损伤增加相对应。这些发现表明，生物钟在IR诱导的DNA损伤和皮肤毒性中起保护作用，可能通过BMAL 1依赖性机制，并可能影响癌症患者中的RT相关放射性皮炎。
Radiation-induced dermatitis is a common occurrence in cancer patients undergoing radiation therapy (RT) and is caused when ionizing radiation (IR) induces DNA strand breaks in skin cells. The wide use of RT in cancer treatments makes it important to minimize RT-induced toxicities including radiodermatitis. This study sought to determine if the circadian clock plays a protective role in minimizing radiodermatitis. We treated mice in control (Day Shift), environmentally-disrupted (Rotating Shift) and genetically-disrupted (Per 1/2−/−) circadian conditions with 6 Gy of IR to the whole body. There was a significantly increased number of radiodermatitis spots on mice with circadian clock disruption compared to control mice. Additionally, circadian clock disrupted mice exhibited reduced protein levels of Bmal1, a phenomenon that sensitized circadian synchronized keratinocytes to IR-induced DNA damage. Furthermore, the skin phenotype results corresponded with significantly reduced body weights and increased genomic DNA damage in blood cells of mice with clock disruption compared to control mice. These findings suggest that the circadian clock plays a protective role in IR-induced DNA damage and skin toxicity, possibly through BMAL1-dependent mechanisms, and potentially impacts RT-associated radiodermatitis in cancer patients.
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DOI：
10.1016/j.jid.2017.10.025
发表时间：
2018-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Slominski AT;Hardeland R;Zmijewski MA;Slominski RM;Reiter RJ;Paus R
通讯作者：
Paus R
影响因子：
6.5
作者：
Spoerl, Florian;Schellenberg, Katja;Kramer, Achim
通讯作者：
Kramer, Achim
DOI：
10.1073/pnas.1215935110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Plikus, Maksim V.;Vollmers, Christopher;Chuong, Cheng-Ming
通讯作者：
Chuong, Cheng-Ming
影响因子：
9.2
作者：
Oklejewicz, Malgorzata;Destici, Eugin;van der Horst, Gijsbertus T. J.
通讯作者：
van der Horst, Gijsbertus T. J.
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U