High levels of 8-hydroxy-2′-deoxyguanosine appear in normal human epidermis after a single dose of ultraviolet radiation

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Abstract
Major photoproducts induced by carcinogenic ultraviolet (UV) radiation are the cylobutane pyrimidine dimers (CPDs) and pyrimidine–pyrimidone (6–4) photoproducts (6–4PPs). 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) is also a DNA base‐modified product generated by reactive oxygen species in conditions of ultraviolet stress. Although UVB‐induced CPDs and 6–4PPs have been investigated in animal and human skin, little is known about the role of 8‐OHdG in UVB‐induced human skin damage or carcinogenesis. Normal human skin from three volunteers was exposed to UV radiation, and the time course of induction and removal of 8‐OHdG was examined by immunohistochemical analysis with catalysed signal amplification on formalin‐fixed paraffin sections. Formation of CPDs and 6–4PPs was also examined by immunostaining on the same skin specimens. Control epidermis with no exposure to UV radiation showed little nuclear staining of 8‐OHdG, but an increased level of 8‐OHdG was clearly observed in epidermis biopsied after irradiation. Induced 8‐OHdG can rapidly be removed from nucleus during the first 24–48 h, as the staining intensity diminished gradually, almost reaching the control level by 72–96 h after irradiation. Staining for CPDs or 6–4PPs revealed induction of these photoproducts in human skin, although 6–4PP‐positive cells disappeared more rapidly than those that stained for CPDs or 8‐OHdG. Together with protective effect of antioxidants, our results indicate that not only CPDs and 6–4PPs but also 8‐OHdG may play a significant part in UV carcinogenesis.

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