Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma.

Amrita Dasgupta,Meena Katdare

doi:10.3390/cancers7030852

Abstract

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

Highlights

Cutaneous Melanoma (CM), the 8th most common cancer in the United States [1] and a leading cause of cancer deaths among young adults, is a type of skin cancer that originates from the malignant transformation of cells called melanocytes in the skin [2,3]
Our results show that White and Hispanic skin melanocytes used in this study have almost the same level of intracellular melanin, implying that HM-GM22253 melanocyte cell line was derived from a lightly pigmented Hispanic subject
Our results demonstrated a reduction in expression of proliferation markers Ki67 and Cyclin D1 (Cy D1) in Hispanic skin melanocytes (Figure 3ii (G–H, K–L)) that correlates with the decrease in cell number observed at 72 h post Ultraviolet radiation (UVR)

Summary

Introduction

Cutaneous Melanoma (CM), the 8th most common cancer in the United States [1] and a leading cause of cancer deaths among young adults, is a type of skin cancer that originates from the malignant transformation of cells called melanocytes in the skin [2,3]. The human skin exhibits a vast variation in the color of skin which is a consequence of the quantity and the quality of melanin pigment in melanocytes [8]. There are three basic types of melanin: eumelanin (darker, brown/black), pheomelanin (lighter, red/yellow), and neuromelanin (dark) [8,11]. The relative amount of eumelanin and pheomelanin is a key determinant of color-based ethnic diversification in humans [12]. Pigmented skin typically contains larger and greater number of melanosomes with higher levels of melanin (eumelanin). Melanin is suggested to render photoprotection from UVR and constitutive levels of melanin in skin may influence UVR-induced CM [19,20]. In addition to differences in constitutive skin pigmentation (relative proportions of eumelanin vs pheomelanin), other risk factors that can influence UVR-induced

Results

Discussion

Conclusion