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Introduction
The omnipresent nature of ultraviolet (UV) radiation in our lives and increasing time spent outdoors has led to a rise in UV-exposure related pathologies. In a 2006 report, the World Health Organization (WHO) estimated that around 1.5 million disability-adjusted life years were lost annually through the direct and indirect effects of excessive UV exposure worldwide [1]. Skin cancer is the predominant pathological manifestation resulting from overexposure to UV radiation, with non-melanoma skin cancers (NMSCs) representing more than 90% of all skin cancers. The WHO recently reported that up to 2–3 million NMSCs are diagnosed worldwide each year, with the USA reporting up to 200,000 new cases of squamous cell carcinoma (SCC) annually, representing 20% of all new skin cancers [1, 2]. Due to reporting requirements, precise figures for NMSCs in Europe are difficult to ascertain, but the literature includes estimates of 78,000 cases annually in the UK, and 41,000 in Germany [3]. New strategies to ameliorate the impact of chronic UV damage and thus skin cancers and photoaging are needed.
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
UV-Mediated Skin Damage
Chronic exposure to solar radiation is the most important environmental factor involved in photoaging and in the pathogenesis of skin cancers, especially actinic keratosis (AK) and SCC. The role of UV radiation in the pathogenesis of basal cell carcinoma (BCC) and melanoma appears more complicated, but is probably related to acute exposure during childhood and adolescence.
Cellular DNA is the major cellular target in UV carcinogenesis, through the induction of photo-induced direct and indirect damage that can induce mutations [4]. The chemical nature and the formation of DNA lesions greatly depend on the wavelength of incident photons. UVB radiation, the most energetic and mutagenic component of solar radiations, is directly absorbed by DNA and induces dimeric photoproducts between adjacent pyrimidine bases, namely cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6–4) pyrimidone (6-4PP) photoproducts (Fig. 1) [5]. A causal relationship has been established between UVB DNA lesions and photocarcinogenesis, as indicated by the high proportion of p53 mutations characterized by cytosine (C)–thymine (T) transitions at dipyrimidine sites and CC–TT tandem base substitutions detected at bipyrimidine sites in skin...