Lahtz Christoph, Kim Sang-In, Bates Steven E, Li Arthur X, Wu Xiwei, Pfeifer Gerd P
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, 91010, USA.
Department of Information Sciences, Beckman Research Institute, City of Hope, Duarte, 91010, USA.
F1000Res. 2013 Feb 13;2:45. doi: 10.12688/f1000research.2-45.v1. eCollection 2013.
Unprotected exposure to UVB radiation from the sun and the resulting DNA damage are thought to be responsible for physiological changes in the skin and for a variety of skin cancers, including basal cell and squamous cell carcinoma and malignant melanoma. Although the mutagenic effects of UVB have been well documented and studied mechanistically, there is only limited information as to whether UV light may also be responsible for inducing epigenetic changes in the genome of exposed cells. DNA methylation is a stable epigenetic modification involved in gene control. To study the effects of UVB radiation on DNA methylation, we repeatedly exposed normal human keratinocytes to a UVB light source. After a recovery period, we analyzed global DNA methylation patterns in the irradiated and control cells using the methylated-CpG island recovery assay (MIRA) method in combination with high-resolution microarrays. Bioinformatics analysis revealed only a limited number of possible differences between UVB-exposed and control cells. However, these minor apparent changes could not be independently confirmed by bisulfite sequencing-based approaches. This study reveals that UVB irradiation of keratinocytes has no recognizable global effect on DNA methylation patterns and suggests that changes in DNA methylation, as observed in skin cancers, are not immediate consequences of human exposure to solar UVB irradiation.
暴露于来自太阳的中波紫外线(UVB)且无防护措施以及由此产生的DNA损伤,被认为是导致皮肤生理变化以及多种皮肤癌的原因,这些皮肤癌包括基底细胞癌、鳞状细胞癌和恶性黑色素瘤。尽管UVB的诱变作用已有充分记录并进行了机制研究,但关于紫外线是否也可能导致暴露细胞基因组发生表观遗传变化的信息却很有限。DNA甲基化是一种参与基因调控的稳定表观遗传修饰。为了研究UVB辐射对DNA甲基化的影响,我们将正常人角质形成细胞反复暴露于UVB光源下。在恢复期后,我们使用甲基化CpG岛回收分析(MIRA)方法结合高分辨率微阵列,分析了照射细胞和对照细胞中的整体DNA甲基化模式。生物信息学分析显示,UVB照射细胞与对照细胞之间只有有限数量的可能差异。然而,这些微小的明显变化无法通过基于亚硫酸氢盐测序的方法独立证实。这项研究表明,角质形成细胞的UVB照射对DNA甲基化模式没有可识别的整体影响,并表明在皮肤癌中观察到的DNA甲基化变化并非人类暴露于太阳UVB辐射的直接后果。