MOLECULAR AND CELLULAR EFFECTS OF ULTRAVIOLET LIGHT-INDUCED GENOTOXICITY

Exposure to the solar ultraviolet spectrum that penetrates the Earth's stratosphere (UVA and UVB) causes cellular DNA damage within skin cel ls. This damage is elicited directly through absorption of energy (UVB ), and indirectly through intermediates such as sensitizer radicals an d reactive oxygen species (UVA), DNA damage is detected as strand brea ks or as base lesions, the most common lesions being 8-hydroxydeoxygua nosine (8OHdG) from UVA exposure and cyclobutane pyrimidine dimers fro m UVB exposure. The presence of these products in the genome may cause misreading and misreplication. Cells are protected by free radical sc avengers that remove potentially mutagenic radical intermediates. In a ddition, the glutathione-S-transferase family can catalyze the removal of epoxides and peroxides. An extensive repair capacity exists for re moving (1) strand breaks, (2) small base modifications (8OHdG), and (3 ) bulky lesions (cyclobutane pyrimidine dimers). UV also stimulates th e cell to produce early response genes that activate a cascade of sign aling molecules (e.g., protein kinases) and protective enzymes (e.g., haem oxygenase). The cell cycle is restricted via p53-dependent and -i ndependent pathways to facilitate repair processes prior to replicatio n and division. Failure to rescue the cell from replication block will ultimately lead to cell death, and apoptosis may be induced. The impl ications for UV-induced genotoxicity in disease are considered.