Oral communication, PS5 / C69

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Two UV pathways to melanoma

SPEAKER F.P. Noonan #whois submiter ?
AUTHOR(s) F.P. Noonan, M.R. Zaidi, A. Wolnicka-Glubisz, M.R. Anver, J. Bahn, A. Wielgus, J. Cadet, T. Douki, S. Mouret, A. Popratiloff, G. Merlino, E.C. De Fabo

The role(s) of UVB (280-320nm) and UVA (320-400nm) in melanoma are unclear but can be addressed in experimental animal models. The hepatocyte growth factor transgenic (HGF/SF) mouse has extrafollicular ectopic melanocytes which are absent in wild-type mice and develops melanomas recapitulating human disease after neonatal UV exposure. We used specialized optical sources to deliver precisely defined UVA or UVB radiation to albino and pigmented HGF/SF transgenic mice and compared melanoma formation. Unexpectedly, the presence of melanin pigment exacerbated melanoma. In pigmented HGF/SF transgenics, melanin was largely confined to melanocytes and protective epidermal melanin was sparse, enabling direct exposure of melanocytes to UV radiation. UVB initiated melanoma and produced cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) quantified by HPLC-MS/MS in neonatal skin independent of pigment status. UVA initiation of CMM, however, was completely dependent on the presence of melanin pigment. UVA irradiation produced only TT-CPDs but at 10-fold lower levels than UVB and melanin did not increase their formation. UVA-induced oxidative DNA damage, however, quantified as nuclear 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo), was found at significantly higher levels in melanocytes in the presence of melanin, both in vivo and in vitro, supporting a photooxidative role for melanin and/or its precursors in UVA melanomagenesis. Our findings have identified two wavelength-dependent pathways to UV-induced melanoma and demonstrate a novel and important role for melanin/melanin precursors in melanoma. These studies also provide experimental support for the epidemiologic associations between solar UV exposure, or use of UVA-emitting tanning lamps and increased melanoma risk.



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Université de Bordeaux 2 & Conseil Régional Aquitaine