UV-Induced DNA Damage and Repair: The Role of Melanin and the MC1R Gene

Title:	UV-Induced DNA Damage and Repair: The Role of Melanin and the MC1R Gene
Author:	Hauser, Jennifer E.
Description:	Malignant melanoma is the most lethal skin cancer. Multiple factors influence melanoma susceptibility, such as the melanocortin 1 receptor (MC1R) gene, cutaneous melanin content, and ultraviolet radiation (UVR) exposure. After irradiating cultured human melanocytes with increasing UVR doses, we examined the influence of melanin content and MC1R function on the induction and repair of DNA photoproducts, particularly cyclobutane pyrimidine dimers (CPD). We analyzed constitutive pigmentation by total melanin content as well as by its components, eumelanin and pheomelanin. In melanocytes expressing functional MC1R, total melanin and eumelanin contents correlated inversely with UVR-induced growth arrest, apoptosis, and CPD induction; however, hydrogen peroxide release was positively correlated. Conversely, melanocytes with loss-of-function MC1R, regardless of total melanin or eumelanin contents, sustained higher levels of UVR-induced apoptosis and CPD induction, with reduced CPD repair capacity. Melanin content, primarily eumelanin content, and MC1R genotype are independent determinants of UVR-induced DNA damage in cultured human melanocytes.
Permanent Link:	http://rave.ohiolink.edu/etdc/view?acc_num=ucin1141335145 http://hdl.handle.net/2374.OX/9575
Date:	2006

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