GENE-EXPRESSION IN SKIN TUMORS INDUCED IN HAIRLESS MICE BY CHRONIC EXPOSURE TO ULTRAVIOLET-B IRRADIATION

We investigated the expressions of c-Ha-ras, c-jun, c-fos, c-myc genes and p53 protein in the development of skin tumors induced by chronic exposure to UVB without a photosensitizer using hairless mice, When mi ce were exposed to UVB at a dose of 2 kJ/m(2) three times a week, incr eased c-Ha-ras and c-myc transcripts were detected after only 5 weeks of exposure, while no tumor appeared on the exposed skin, The increase in gene expression continued until 25 weeks, when tumors, identified pathologically as mainly squamous cell carcinomas (SCC), developed in the dorsal skin, In these SCC, overexpression of c-fos mRNA was also o bserved along with the increases in c-Ha-ras and c-myc, A single dose of UVB (2 kJ/m(2)) applied to the backs of hairless mice transiently i nduced overexpression of the early event genes c-fos, c-jun and c-myc, but not c-Ha-ras, in the exposed area of skin, Accumulation of p53 pr otein was determined by Western blotting analysis or immunohistochemis try using monoclonal antibodies PAb 240 or 246, which recognize mutant or wild type, respectively, In the SCC, a mutant p53 protein accumula ted in the cytoplasm and nucleus, After single-dose irradiation, the i ncreased wild-type p53 protein was observed in the nuclei of epidermal cells, The present results suggest that overexpression of the c-fos, c-myc and c-aa-ras genes, and the mutational changes in p53 protein mi ght be associated with skin photocarcinogenesis, Moreover, overexpress ion of the c-Ha-ras and c-myc genes might be an early event in the dev elopment of UVB-induced skin tumors in mice.