Fate of UVB-induced p53 mutations in SKH-hr1 mouse skin after discontinuation of irradiation: Relationship to skin cancer development

Vladislava O. Melnikova, Alessia Pacifico, Sergio Chimenti, Ketty Peris, Honnavara N. Ananthaswamy

Research output: Contribution to journalArticle

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 p53V154A/R155C, p53 H175H/H176Y, and p53R275C mutant alleles remained at or near 100%, whereas the percentage of mice with p53R270C mutation decreased by 45%. As expected, discontinuation of UVB after 8 weeks resulted in a delay in tumor development. A 100% of tumors carried p53V154A/R155C mutant alleles, 76% carried p53H175H/H176Y mutants, and 24 and 19% carried p53R270C and p53R275C 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.

Original languageEnglish
Pages (from-to)7055-7063
Number of pages9
JournalOncogene
Volume24
Issue number47
DOIs
Publication statusPublished - Oct 27 2005

    Fingerprint

Keywords

  • Differentiation
  • p53
  • Skin tumor
  • Tumor progression
  • UVB carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this