The use of metabolic inhibitors to compare the excision repair of pyrimidine dimers and nondimer DNA damages in human skin fibroblasts exposed to 254-nm and sunlamp-produced greater than 310-nm ultraviolet radiation.

Abstract

Normal human skin fibroblasts were exposed to either 0-5 J/m2 of 254-nm ultraviolet (UV) radiation or 0-50 kJ/m2 of the Mylar-filtered UV (greater than 310 nm) produced by a fluorescent sunlamp. These cells were then incubated for 0-20 min in medium containing 10 mM hydroxyurea (HU) and 0.1 mM 1-beta-D-arabinofuranosyl cytosine (ara C), and the yield of DNA strand breaks was measured by means of the alkaline elution technique. For cells irradiated with 254-nm UV, which results primarily in the formation of cyclobutane pyrimidine dimers, a rapid increase in DNA strand breaks was detected following incubation with these metabolic inhibitors. In contrast, only a low level of strand breaks formed in cells incubated with HU and ara C after irradiation with approximately equitoxic fluences of sunlamp UV greater than 310 nm, which mainly causes the induction of nondimer DNA lesions. Hence, these results are consistent with the conclusion that the pathways involved in the repair of nondimer DNA damages induced by UV wavelengths greater than 310 nm differ from the repair of pyrimidine dimers.