Chronic ultraviolet exposure-induced p53 gene alterations in Sencar mouse skin carcinogenesis model

• Published in: Journal of toxicology and environmental health Vol. 51; no. 3; p. 219
• Main Authors: Tong, Y, Smith, M A, Tucker, S B
• Format: Journal Article
• Language: English
• Published: United States 27.06.1997
• Subjects: Animals; Carcinoma - genetics; Carcinoma, Squamous Cell - genetics; Cell Nucleus; Disease Models, Animal; DNA - genetics; DNA - isolation & purification; Exons; Female; Gene Amplification - genetics; Gene Amplification - radiation effects; Genes, p53 - genetics; Genes, p53 - radiation effects; Humans; Immunohistochemistry; Mice; Mice, Inbred SENCAR; Neoplasms, Radiation-Induced - genetics; Papilloma - genetics; Paraffin Embedding; Point Mutation - genetics; Point Mutation - radiation effects; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Reference Standards; Skin - radiation effects; Skin Neoplasms - genetics; Ultraviolet Rays - adverse effects
• ISSN: 0098-4108
• DOI: 10.1080/00984109708984023

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.