Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Fairborn, OH 45435, USA.
Int J Mol Sci. 2021 Jun 6;22(11):6112. doi: 10.3390/ijms22116112.
Skin cancers are growing in incidence worldwide and are primarily caused by exposures to ultraviolet (UV) wavelengths of sunlight. UV radiation induces the formation of photoproducts and other lesions in DNA that if not removed by DNA repair may lead to mutagenesis and carcinogenesis. Though the factors that cause skin carcinogenesis are reasonably well understood, studies over the past 10-15 years have linked the timing of UV exposure to DNA repair and skin carcinogenesis and implicate a role for the body's circadian clock in UV response and disease risk. Here we review what is known about the skin circadian clock, how it affects various aspects of skin physiology, and the factors that affect circadian rhythms in the skin. Furthermore, the molecular understanding of the circadian clock has led to the development of small molecules that target clock proteins; thus, we discuss the potential use of such compounds for manipulating circadian clock-controlled processes in the skin to modulate responses to UV radiation and mitigate cancer risk.
皮肤癌的发病率在全球范围内呈上升趋势,主要是由于暴露于紫外线(UV)波长的阳光。紫外线辐射会在 DNA 中诱导形成光产物和其他损伤,如果不通过 DNA 修复去除,可能会导致突变和癌变。尽管导致皮肤癌变的因素已经得到了很好的理解,但过去 10-15 年的研究已经将紫外线暴露的时间与 DNA 修复和皮肤癌变联系起来,并暗示了生物钟在紫外线反应和疾病风险中的作用。在这里,我们回顾了已知的皮肤生物钟,它如何影响皮肤生理学的各个方面,以及影响皮肤昼夜节律的因素。此外,对生物钟的分子理解导致了靶向时钟蛋白的小分子的开发;因此,我们讨论了这些化合物在操纵皮肤中生物钟控制的过程以调节对紫外线辐射的反应和降低癌症风险方面的潜在用途。