Individual Photosensitivity of Human Skin and UVA-Induced Pyrimidine Dimers in DNA

Abstract

Delineation of the DNA-damaging properties of UVA radiation is a major issue in understanding solar carcinogenesis. Emphasis was placed in this study on the formation of cyclobutane pyrimidine dimers (CPDs), which are now well established as the most frequent UVA-induced DNA lesions in human skin. The yield of CPDs was determined by a chromatographic assay following ex vivo UVA and UVB irradiation of biopsies taken from either phototype II or IV volunteers. A clear correlation was found between the frequency of UVB-induced CPDs and both the phototype and the minimum erythemal dose (MED). Similar results were obtained for the induction of CPDs upon exposure to UVA. Moreover, an excellent correlation was observed for each donor between the yield of DNA damage induced by either UVB or UVA. These observations show that the key parameters driving UVA-induced formation of CPDs are attenuation of radiation in the skin and the number of photons reaching skin cells rather than the cellular content in photosensitizers. In addition, the results show that both MED and phototype are good predictors of the vulnerability of DNA toward UVB and UVA in the skin. This result is of importance for the identification of individuals to be extensively protected.

A new hair follicle-derived human epidermal model for the evaluation of sunscreen genoprotection

“…2 represents the inter-individual variation more than the reproducibility and the accuracy of the detection. A similar observation has been previously made in the HPLC-MS/MS quantification of TT CPD in human biopsies exposed to either UVB or UVA [47]. The data also show the strong similarity in the distribution of the different photoproducts between human skin explant and RHE model.…”

DNA Base Damage by Reactive Oxygen Species, Oxidizing Agents, and UV Radiation

“…T and, to a lesser extent, T ,. C are generated (but not 6-4PPs) in fibroblasts, keratinocytes, melanocytes, and human skin (Mouret et al 2006(Mouret et al , 2008(Mouret et al , 2011. Histoimmunochemical measurements confirmed the presence of CPDs in the epidermis, whereas 6-4PPs were not detected (Tewari et al 2012).…”

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions†

“…In fact, UVA radiation has been shown since the 1970s, first in bacteria (29) and then in mammalian cells (32,55,(80)(81)(82)(83)(84) and human skin (61,65,(85)(86)(87), to be also able to induce CPDs. However, these observations have been poorly considered until recently.…”