title: p53 mutations as a marker of skin cancer risk: comparison of UVA and UVB effects.
abstract: The epidermis is excellently adapted to the sun's ultraviolet (UV) radiation. The p53 protein plays a crucial role in the orchestration of a cell's response to UV-induced damage, and more specifically to DNA damage. This response appears to differ between differentiated (suprabasal) and undifferentiated (basal) epidermal cells. The latter are the most likely targets in UV carcinogenesis. The UVB-related mutations in p53 genes of human carcinomas from sun-exposed skin indicate that rendering p53 dysfunctional is an important (early) step in the formation of these tumors. Experiments in hairless mice confirm this finding for UVB-driven carcinogenesis, but not for UVA1-(365-nm)-driven carcinogenesis. Microscopic clusters of preneoplastic cells overexpressing mutant p53 occur in chronically UVB-exposed murine skin long before the ultimate carcinomas. The number of these clusters at a certain time-point appears to be predictive of the tumor risk at latter time-points. These UVB-induced p53 clusters appear to be suitable surrogates of tumors in short-term experiments.
authors.affiliation: Department of Dermatology, Sylvius Laboratories, Room 3038, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 Leiden, The Netherlands. F.R.de.Gruijl@lumc.nl
authors.forename: Frank R
authors.initials: FR
authors.lastname: de Gruijl
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D016158:Genes, p53 / Q000528:radiation effects*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D014408:Biomarkers, Tumor