RESUMO
The role of UVA-radiation-the major fraction in sunlight-in human skin carcinogenesis is still elusive. We here report that different UVA exposure regime (4 x 5 J/cm(2) per week or 1 x 20 J/cm(2) per week) caused tumorigenic conversion (tumors in nude mice) of the HaCaT skin keratinocytes. While tumorigenicity was not associated with general telomere shortening, we found new chromosomal changes characteristic for each recultivated tumor. Since this suggested a nontelomere-dependent relationship between UVA irradiation and chromosomal aberrations, we investigated for alternate mechanisms of UVA-dependent genomic instability. Using the alkaline and neutral comet assay as well as gamma-H2AX foci formation on irradiated HaCaT cells (20-60 J/cm(2)), we show a dose-dependent and long lasting induction of DNA single and double (ds) strand breaks. Extending this to normal human skin keratinocytes, we demonstrate a comparable damage response and, additionally, a significant induction and maintenance of micronuclei (MN) with more acentric fragments (indicative of ds breaks) than entire chromosomes particularly 5 days post irradiation. Thus, physiologically relevant UVA doses cause long-lasting DNA strand breaks, a prerequisite for chromosomal aberration that most likely contribute to tumorigenic conversion of the HaCaT cells. Since normal keratinocytes responded similarly, UVA may likewise contribute to the complex karyotype characteristic for human skin carcinomas.
Assuntos
Transformação Celular Neoplásica , Aberrações Cromossômicas , Dano ao DNA , Queratinócitos/efeitos da radiação , Queratinócitos/ultraestrutura , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Linhagem Celular Tumoral , Cromossomos/efeitos da radiação , Ensaio Cometa , Humanos , Hibridização in Situ Fluorescente , Camundongos , Camundongos Nus , Testes para Micronúcleos , Transplante de Neoplasias , Pele/citologiaRESUMO
Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin disease characterized by circulating IgA antibodies binding the basement membrane zone. In most cases the origin is not clear, but in a minority of cases LABD is drug induced. We describe a patient in whom linear IgA disease developed shortly after beginning therapy with atorvastatin. In Western blotting analysis we detected IgA and IgG class antibodies targeting a 97-kd protein. To our knowledge this is the first reported case of atorvastatin-induced LABD.
