Jul 11, 2006

Melanin content and MC1R function independently affect UVR-induced DNA damage in cultured human melanocytes

Pigment Cell Research
Jennifer HauserZalfa A Abdel-Malek

Abstract

Malignant transformation of melanocytes leads to melanoma, the most fatal form of skin cancer. Ultraviolet radiation (UVR)-induced DNA photoproducts play an important role in melanomagenesis. Cutaneous melanin content represents a major photoprotective mechanism against UVR-induced DNA damage, and generally correlates inversely with the risk of skin cancer, including melanoma. Melanoma risk is also determined by susceptibility genes, one of which is the melanocortin 1 receptor (MC1R) gene. Certain MC1R alleles are strongly associated with melanoma. We hereby present experimental evidence for the role of two melanoma risk factors, constitutive pigmentation, as assessed by total melanin, eumelanin and pheomelanin contents, and MC1R genotype and function, in determining the induction and repair of DNA photoproducts in cultured human melanocytes after irradiation with increasing doses of UVR. We found that total melanin and eumelanin contents (MC and EC) correlated inversely with the extent of UVR-induced growth arrest, apoptosis and induction of cyclobutane pyrimidine dimers (CPD), but not with hydrogen peroxide release in melanocytes expressing functional MC1R. In comparison, melanocytes with loss-of-function MC1R, regardless of ...Continue Reading

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Citations

Mentioned in this Paper

Malignant Neoplasm of Skin
Melanocyte
Hydrogen Peroxide
Apoptosis, Intrinsic Pathway
MC1R Protein
Base Excision Repair
Phaeomelanins
Melanoma vaccine
Cell Division Phases
Apoptosis

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