The skin and barrier function in radiation and chemical exposures

Abstract

Sunscreens provide protection against ultraviolet radiation (UV), UVB and more recently UVA rays. The active ingredients within sunscreen formulations can broadly be divided into either the chemical absorbers or physical filters. Titanium dioxide (TiO2), a commonly used physical filter compound, has been shown to exhibit size dependent reactivity properties when primary particles are within the nano-range (one or more dimensions being within 1-100nm in size). Such effects are suspected to contribute to the disruption of the skins barrier function following topical application. The ability of solar UV to induce skin cancer and photoageing effects is well recognised. The effect of the infrared (IR) and the visible light (VIS) components of solar radiation on skin and their interaction with UV is however lesser known. Skin fibroblast and keratinocyte cells in monolayer were exposed to physiologically relevant doses of solar light. Biomarkers of damage including reactive oxygen species (ROS) generation, mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage were assessed. Further to this the apparent toxicological effects of TiO2 on skin cells were investigated through the assessment of cell viability, ROS generation, and nDNA damage in the form of double strand breaks. The effect of TiO2 on the perturbation of skin barrier function was also investigated by measuring the percutaneous absorption of a marker compound radiolabelled (1-methyl 14C) caffeine through human skin. Absorption studies were carried out in the presence or absence of TiO2 plus or minus solar UV. Data obtained within this thesis indicate that the individual action of IR, VIS or UV alone have marginal effects on the level of biomarkers of damage detected. When applied simultaneously, complete solar light was found to produce a synergistic effect significantly greater than the cellular stress responses detected from the individual components. Similarly, blocking the UVB and a portion of the UVA rays from complete solar light appeared to reduce the level of ROS generation, albeit the synergistic action of solar light could still be observed. Sunscreens, both commercially relevant formulations and TiO2 dispersions, were found to provide protection against solar light exposures in vitro. When assessed under cell culture conditions TiO2 was seen to induce significant ROS generation and nDNA damage following the application of solar UV. No effects of TiO2 were however detected when the absorption 3 of the marker compound was assessed. The data presented suggest a further need for broad spectrum protection within sunscreen formulations. Furthermore although the work identifies potential harmful effects arising from the TiO2 compound, the human skin explants assessed in the study were able to maintain a natural skin barrier function following exposure to TiO2 plus or minus solar UV.