No major role for 7,8-dihydro-8-oxoguanine in ultraviolet light-induced mutagenesis

Oxidative DNA damage, in particular 7,8-dihydro-8-oxoguanine (8-oxoG), has been suggested to mediate mutation formation and malignant transformation after exposure of the skin to long-wave ultraviolet (UVA) light. It is processed primarily by the base excision repair (BER) pathway. The initial step of BER is the removal of the damaged base by a damage-specific DNA-glycosylase, which is 8-oxoG DNA glycosylase (OGG1) for 8-oxoG. To study the contribution of 8-oxoG to UVA-light mutagenesis, we compared UVA- and UVB-light-induced mutation frequencies in mouse embryonal fibroblasts from OGG1 knockout mice and their OGG1-intact littermates using the ouabain mutagenesis assay. After irradiation with various doses of UVA or UVB radiation, mutations in the Na,K-ATPase gene of single cells were detected by testing for colony-forming ability in a selective medium. OGG1-/- cells did not exhibit an increased frequency of UV-light-induced mutations compared to OGG1+/+ cells after exposure to either UVA or UVB radiation. This indicates that 8-oxoG, which is processed by OGG1, does not contribute significantly to either UVA- or UVB-light-induced mutagenesis.