The circadian clock protects against acute radiation-induced dermatitis
| Autor: | Shobhan Gaddameedhi, Panshak P. Dakup, Kenneth I. Porter |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Keratinocytes DNA damage medicine.medical_treatment Circadian clock Toxicology 03 medical and health sciences Mice 0302 clinical medicine Circadian Clocks Neoplasms medicine Radiodermatitis Animals Circadian rhythm Pharmacology Mice Hairless business.industry Radiation-Induced Dermatitis Cancer ARNTL Transcription Factors medicine.disease Circadian Rhythm Radiation therapy 030104 developmental biology 030220 oncology & carcinogenesis Toxicity Cancer research Female business DNA Damage |
| Zdroj: | Toxicology and applied pharmacology. 399 |
| ISSN: | 1096-0333 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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