Human skin keratinocytes exposed to blue light: damage on nuclear DNA and genome instability

Abstract

The skin is the main physical barrier against environmental and biological agents, as well as preventing dehydration. Skin is exposed every day to solar radiation causing cellular changes due to photosensitization processes by which the excited molecule by photons transfers its excitation energy to a neighboring molecule, returning to its ground state. This molecule that absorbs light and transfers its energy to other molecules is called a photosensitizer (e.g., flavins, melanin, lipofuscin, carotenoids). It can be endogenous or exogenous and reacts with other molecules of its surroundings through two main types of mechanisms: type I and type II. The visible light is one of the existing radiations in the solar spectrum that promotes this type reaction and although it has a brief knowledge in the literature, it comprises 43% of all energy of the solar radiation that arrives at the terrestrial surface and has a high power of penetration in the human skin. There are several types of cellular changes that can occur through the photosensitization reaction, however, the focus of this project will be the formation of possible damage to the DNA, which correspond to the chemical and physical changes in the DNA structure, such as base oxidation (e.g., 8-oxo-dG) and covalent bonds between adjacent bases (pyrimidine dimers), resulting in genomic instability, compromising the replication and transcription processes, if not repaired leading to the mutations. These modifications are involved with skin cancers, such as melanoma and squamous cell carcinoma. We have investigated the effects of blue light in HaCaT cells (skin human keratinocytes), detecting 8-oxo-dG accumulation (premutagenic lesion) and DNA strands breaks. Thus, in this work, we will aim to identify alterations in the level of some proteins involved in DNA repair signaling, which are responsible for avoiding serious mutagenic events, such as phosphorylated H2AX, an example of a key factor in the process of repairing DNA double-strand breaks and PARP-1 used for repair of single-stranded DNA strand breaks. There is no result in the literature reporting the DNA repair signaling for visible light. Therefore, these data will provide new information of mutagenic potential of blue light, indicating the relevance for a new paradigm of skin protection against the dangerous effects of visible light.