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Ultraviolet Radiation Induction of Squamous Cell Carcinomas in p53 Transgenic Mice¹

Division of Dermatology [G. L., V. C. H., V. A. T.] and Department of Pathology [G. L., K. B., V. A. T.], British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada

Mutations of the p53 gene have been implicated in the pathogenesis of cutaneous squamous cell carcinoma (SCC). To examine the role of p53 in skin carcinogenesis, we observed the development of skin cancers in p53 transgenic mice which carry multiple copies of a mutant allele of the p53 gene with or without chronic UVB radiation. Thirty-one tumors developed in 19 UV-irradiated p53 transgenic mice versus 14 of 19 in the control group; 9 p53 transgenic mice but none of the control mice developed multiple tumors. Histologically, 14 of 14 tumors in the CD-1 mice were SCCs. In the p53 transgenic mice, 25 of 31 tumors were SCCs, and 6 were benign tumors. The mean time to appearance of tumors did not differ between CD-1 mice (26.3 weeks) and the p53 transgenic mice (25.7 weeks; P = 0.512). The p53 protein, which was undetectable by immunohistochemistry in the keratinocytes of CD-1 mice, was elevated in 93% (13 of 14) of tumors from CD-1 mice. These data indicate that mutation of the p53 gene is an important step in the development of SCC. p53 mutations do not alter the latent period of UV-induced SCC but significantly increase the number of tumors and the propensity for multiple tumor development.

¹ This study was supported by Grant 106(93-1) from B.C. Health Research Foundation.

² To whom requests for reprints should be addressed, at Skin Cancer Research Laboratory, B.C. Cancer Research Centre, 601 W. 10th Avenue, Vancouver, BC V5Z 1L3, Canada.

Received 8/15/94. Accepted 3/15/95.

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