The Role of Singlet Oxygen in the UVA‐Induced Bystander Effect on Dermal Fibroblasts

Chronic sun exposure results in photoaging manifested as wrinkles, furrows, and loss of skin elasticity. Dermal collagen becomes fragmented and crosslinked, glycosaminoglyan levels increase and elastosis becomes prevalent. These alterations are the result of modifications to proteins, lipids and nucleic acids by reactive oxygen species (ROS) generated by UVA/B exposure of dermal photosensitizers. In the current work we demonstrate that collagen exposed to UVA generates both hydrogen peroxide and singlet oxygen (1O2) and that fibroblasts exposed to this environment increase their expression of MMP‐1 (> 4 J/cm2), undergo cell senescence (> 10 J/cm2) and at high exposure levels undergo cell death (> 10J/cm2). Based upon the partial inhibition of cell death by catalase, and the ability of sodium azide to inhibit and deuterium oxide to enhance UVA‐mediated necrosis/apoptosis, both ROS appear to contribute to this UVA effects. The contribution of 1O2 to apoptosis/necrosis is further verified by the requirement for cell contact with collagen during irradiation. We further demonstrate that sensitivity to UVA does not require collagen‐mediated changes in fibroblasts that alter sensitivity to ROS. Taken together these results support the notion that the reduction in collagen at the fibroblast plasma membrane, which typifies sun damaged dermis, may have evolved as an adaptive response.