title: Molecular and cellular effects of ultraviolet light-induced genotoxicity.
abstract: Exposure to the solar ultraviolet spectrum that penetrates the Earth's stratosphere (UVA and UVB) causes cellular DNA damage within skin cells. This damage is elicited directly through absorption of energy (UVB), and indirectly through intermediates such as sensitizer radicals and reactive oxygen species (UVA). DNA damage is detected as strand breaks or as base lesions, the most common lesions being 8-hydroxydeoxyguanosine (8OHdG) from UVA exposure and cyclobutane pyrimidine dimers from UVB exposure. The presence of these products in the genome may cause misreading and misreplication. Cells are protected by free radical scavengers that remove potentially mutagenic radical intermediates. In addition, the glutathione-S-transferase family can catalyze the removal of epoxides and peroxides. An extensive repair capacity exists for removing (1) strand breaks, (2) small base modifications (8OHdG), and (3) bulky lesions (cyclobutane pyrimidine dimers). UV also stimulates the cell to produce early response genes that activate a cascade of signaling molecules (e.g., protein kinases) and protective enzymes (e.g., haem oxygenase). The cell cycle is restricted via p53-dependent and -independent pathways to facilitate repair processes prior to replication and division. Failure to rescue the cell from replication block will ultimately lead to cell death, and apoptosis may be induced. The implications for UV-induced genotoxicity in disease are considered.
authors.affiliation: Aston University, Birmingham, UK.
authors.forename: H R
authors.initials: HR
authors.lastname: Griffiths
authors.forename: P
authors.initials: P
authors.lastname: Mistry
authors.forename: K E
authors.initials: KE
authors.lastname: Herbert
authors.forename: J
authors.initials: J
authors.lastname: Lunec
mesh_terms: D000818:Animals; D000975:Antioxidants; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D005609:Free Radicals; D006801:Humans; D012867:Skin / Q000737:chemistry*; D012878:Skin Neoplasms / Q000209:etiology; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D004247:DNA