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

Hacker, E, Muller, HK, Hayward, N, Fahey, P and Walker, G (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: 121-128. doi:10.1111/j.1755-148X.2009.00643.x

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Author Hacker, E
Muller, HK
Hayward, N
Fahey, P
Walker, G
Title Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C⁄R24C⁄Tyr-NrasQ61K mice following neonatal UVR
Formatted title
Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C⁄R24C⁄Tyr-NrasQ61K mice following neonatal UVR
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
Publication date 2010-02
Year available 2009
Sub-type Article (original research)
DOI 10.1111/j.1755-148X.2009.00643.x
Volume 23
Issue 1
Start page 121
End page 128
Total pages 8
Place of publication Malden, MA, U.S.A.
Publisher Wiley-Blackwell Publishing
Collection year 2011
Language eng
Subject C1
920102 Cancer and Related Disorders
110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)
110304 Dermatology
Formatted abstract
To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C ⁄ R24CNrasQ61K 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.
© 2009 John Wiley & Sons A/S
Keyword Melanoma
Ultraviolet radiation
Melanocyte activation
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Additional Notes Article first published online: 24 September 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
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