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Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4 R24C/R24C /Tyr‐Nras Q61K mice following neonatal UVR
Author(s) -
Hacker Elke,
Muller H. Konrad,
Hayward Nicholas,
Fahey Paul,
Walker Graeme
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00643.x
Subject(s) - neuroblastoma ras viral oncogene homolog , dna , endonuclease , microbiology and biotechnology , melanoma , nuclease , dna repair , chemistry , cancer research , genetics , biology , mutation , gene , kras
Summary To further investigate the use of DNA repair‐enhancing agents for skin cancer prevention, we treated Cdk4 R24C/R24C /Nras Q61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal‐cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine‐treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR‐initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.