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Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

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.

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Abstract

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.

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7 citations in Web of Science®

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ID Code: 30123
Item Type: Journal Article
Keywords: Melanoma, DNA Repair, Ultraviolet Radiation, Dimericine, Melanocyte Activation
DOI: 10.1111/j.1755-148X.2009.00643.x
ISSN: 1755-1471
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Public Health & Social Work
Copyright Owner: Copyright 2010 Blackwell Munksgaard
Deposited On: 01 Feb 2010 11:33
Last Modified: 01 Mar 2012 00:05

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