title: Chronic ultraviolet exposure-induced p53 gene alterations in Sencar mouse skin carcinogenesis model.
abstract: Alterations of the tumor suppresser gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10/37 (27%) of SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C-->A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C-->T, two C-->A, one C-->G, and one A-->T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin.
authors.affiliation: Clayton Foundation for Research, Houston, Texas, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: S B
authors.initials: SB
authors.lastname: Tucker
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002467:Cell Nucleus; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D005784:Gene Amplification / Q000235:genetics / Q000528:radiation effects; D016158:Genes, p53 / Q000235:genetics / Q000528:radiation effects*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018632:Mice, Inbred SENCAR; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D010212:Papilloma / Q000235:genetics; D016612:Paraffin Embedding; D017354:Point Mutation / Q000235:genetics / Q000528:radiation effects; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012015:Reference Standards; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D004247:DNA