1. ¹Department of Immunology, The University of Texas MD Anderson Cancer Center, PO Box 301402, Unit 902, Houston, TX 77030, USA
2. ²Department of Dermatology, The University of Rome 'tor Vergata', Rome, Italy
3. ³Department of Dermatology, The University of l'Aquila, L'Aquila 67100, Italy

Correspondence: HN Ananthaswamy, E-mail: hanantha@mdanderson.org

⁴These authors contributed equally to this work

⁵Current address: Department of Dermatology, The University of l'Aquila, L'Aquila, Italy

Received 10 February 2005; Revised 6 April 2005; Accepted 28 April 2005; Published online 11 July 2005.

Abstract

Chronic exposure to ultraviolet (UV) radiation causes skin cancer in humans and mice. We have previously shown that in hairless SKH-hr1 mice, UVB-induced p53 mutations arise very early, well before tumor development. In this study, we investigated whether discontinuation of UVB exposure before the onset of skin tumors results in the disappearance of p53 mutations in the skin of hairless SKH-hr1 mice. Irradiation of mice at a dose of 2.5 kJ/m² three times a week for 8 weeks induced p53 mutations in the epidermal keratinocytes of 100% of the mice. UVB irradiation was discontinued after 8 weeks, but p53 mutations at most hotspot codons were still present even 22 weeks later. During that period, the percent of mice carrying p53^V154A/R155C, p53^H175H/H176Y, and p53^R275C mutant alleles remained at or near 100%, whereas the percentage of mice with p53^R270C mutation decreased by 45%. As expected, discontinuation of UVB after 8 weeks resulted in a delay in tumor development. A 100% of tumors carried p53^V154A/R155C mutant alleles, 76% carried p53^H175H/H176Y mutants, and 24 and 19% carried p53^R270C and p53^R275C mutants, respectively. These results suggest that different UVB-induced p53 mutants may provide different survival advantages to keratinocytes in the absence of further UVB exposure and that skin cancer development can be delayed but not prevented by avoidance of further exposure to UVB radiation.