Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR
Data(s) |
24/09/2010
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Resumo |
To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C/R24C/NrasQ61K 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. |
Formato |
application/pdf |
Identificador | |
Publicador |
Wiley-Blackwell Munksgaard |
Relação |
http://eprints.qut.edu.au/30123/1/c30123.pdf DOI:10.1111/j.1755-148X.2009.00643.x Hacker, Elke, Muller, Konrad, Hayward, Nicholas K., Fahey, Paul, & Walker, Graeme J. (2010) Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR. Pigment Cell and Melanoma Research, 23(1), pp. 121-128. |
Direitos |
Copyright 2010 Blackwell Munksgaard |
Fonte |
Faculty of Health; Institute of Health and Biomedical Innovation; School of Public Health & Social Work |
Palavras-Chave | #111201 Cancer Cell Biology #Melanoma #DNA Repair #Ultraviolet Radiation #Dimericine #Melanocyte Activation |
Tipo |
Journal Article |