title: Zebrafish have a competent p53-dependent nucleotide excision repair pathway to resolve ultraviolet B-induced DNA damage in the skin.
abstract: Ultraviolet (UV) light is a primary environmental risk factor for melanoma, a deadly form of skin cancer derived from the pigmented cells called melanocytes. UVB irradiation causes DNA damage, mainly in the form of pyrimidine dimers (cis-syn cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts), and organisms have developed complex multiprotein repair processes to cope with the DNA damage. Zebrafish is becoming an important model system to study the effects of UV light in animals, in part because the embryos are easily treated with UV irradiation, and the DNA damage repair pathways appear to be conserved in zebrafish and mammals. We are interested in exploring the effects of UV irradiation in young adult zebrafish, so that we can apply them to the study of gene-environment interactions in models of skin cancer. Using the Xiphophorus UV melanoma model as a starting point, we have developed a UV irradiation treatment chamber, and established UV treatment conditions at different ages of development. By translating the Xiphophorus UV treatment methodology to the zebrafish system, we show that the adult zebrafish skin is competent for nucleotide excision DNA damage repair, and that like in mammalian cells, UV treatment promotes phosphorylation of H2AX and a p53-dependent response. These studies provide the groundwork for exploring the role of UV light in melanoma development in zebrafish.
authors.affiliation: Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Edinburgh Cancer Research Centre, The University of Edinburgh, Edinburgh, UK.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zeng
authors.forename: Jennifer
authors.initials: J
authors.lastname: Richardson
authors.forename: Daniel
authors.initials: D
authors.lastname: Verduzco
authors.forename: David L
authors.initials: DL
authors.lastname: Mitchell
authors.forename: E Elizabeth
authors.initials: EE
authors.lastname: Patton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000528:radiation effects; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D016159:Tumor Suppressor Protein p53