oa DNA Damage and Apoptotic Signaling Following Sunlight

Sunlight induces DNA damage due to the ultraviolet (UV) components UVA and UVB. Pyrimidine dimers (CPDs and 6-4PPs) are the most toxic lesions induced by sunlight, and are mainly induced by UVB light, although these lesions are also potentially induced by UVA. On the other hand, UVA light is known to indirectly generate oxidative species, which also damage DNA. By using DNA repair deficient cell lines from xeroderma pigmentosum (XP) patients, expressing pyrimidine-dimer-specific photolyases, we investigated the biological relevance of these lesions in cell killing induction after UVA-irradiation. The results clearly indicate that both CPDs and 6-4PPs are important lesions inducing cell killing, including apoptosis, although other lesions also participate in the events that lead to cell death by UVA. XP cell lines were also employed as sensitive cell targets for the development of sunlight cell dosimeter, which can be useful to analyze the ability of sunscreen filters to protect them from irradiation. Again, although sunscreen filters provided some cell protection from the ability to induce pyrimidine dimers, other types of DNA damage (probably mainly related to UVA) also efficiently induce cell death, reducing the protection factor of normally employed sunscreen filters. Thus, DNA lesions probably induced by oxidative reactive species are also biologically relevant when considering sunlight effects in human cells, and these lesions are also important when considering the sensitivity of XP patients.