UV-induced oxidative stress and photoaging

Chronic UV exposure causes photoaging including skin cancer, solar lentigo and wrinkle. UV-induced oxidative stress is closely related to photoaging. Thus far, UVB-induced DNA damage has been paid much attention in view of photocarcinogenesis. Direct absorption of UVC or UVB leads to formation of cyclobutane-type pyrimidine dimers and pyrimidine pyrimidone (6-4) photoproducts at adjacent pyrimidines. Previous studies suggested that pyrimidine photoproducts are the major classes of UV-induced DNA lesions involved in the cytotoxicity and mutagenesis. Pyrimidine photoproducts induce preferentially transition-type base changes especially at dipyrimidine sites, sometimes called as UV-signature mutations. However, recent reports indicate the involvement of other molecules. UVB induces not only pyrimidine photoproducts but also oxidative DNA damage. Several reports pointed out that types of mutations that are not theoretically caused by pyrimidine photoproducts are frequently observed in the human skin cancers of sun-exposed areas and UVB-induced murine skin cancers. Recent studies have shown that not only UVB but also UVA is involved in photocarcinogenesis based on animal experiments. UVA can induce indirect DNA damage via ROS and lipid peroxidation. ROS have been associated not only with initiation, but promotion and progression in the multistage carcinogenesis model. We have demonstrated that Ogg1 knockout mice, which cannot repair 8-oxoG, representative oxidative DNA damage, is susceptible to photocarcinogenesis. Photoaging is induced via response of epidermal cells or dermal fibroblasts to both UVB and UVA and its signal transduction in the epidermal cells and dermal cells develop photoaging. In order to reduce photoaging we should clarify the mechanisms how UVA and UVB cause cellular response.