Title | Cell-intrinsic melanin fails to protect melanocytes from ultraviolet-mutagenesis in the absence of epidermal melanin. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Weiss TJ, Crawford ER, Posada V, Rahman H, Liu T, Murphy BM, Arnold TE, Gray S, Hu Z, Hennessey RC, Yu L, D'Orazio JA, Burd CJ, Zippin JH, Grossman D, Burd CE |
Journal | Pigment Cell Melanoma Res |
Volume | 36 |
Issue | 1 |
Pagination | 6-18 |
Date Published | 2023 Jan |
ISSN | 1755-148X |
Keywords | Animals, Melanins, Melanocytes, Melanoma, Mice, Mice, Inbred C57BL, Mutagenesis, Skin Neoplasms, Ultraviolet Rays |
Abstract | Melanin is a free-radical scavenger, antioxidant, and broadband absorber of ultraviolet (UV) radiation which protects the skin from environmental carcinogenesis. However, melanin synthesis and UV-induced reactive melanin species are also implicated in melanocyte genotoxicity. Here, we attempted to reconcile these disparate functions of melanin using a UVB-sensitive, NRAS-mutant mouse model, TpN. We crossed TpN mice heterozygous for an inactivating mutation in Tyrosinase to produce albino and black littermates on a C57BL/6J background. These animals were then exposed to a single UVB dose on postnatal day three when keratinocytes in the skin have yet to be melanized. Approximately one-third (35%) of black mice were protected from UVB-accelerated tumor formation. However, melanoma growth rates, tumor mutational burdens, and gene expression profiles were similar in melanomas from black and albino mice. Skin from albino mice contained more cyclobutane pyrimidine dimer (CPD) positive cells than black mice 1-h post-irradiation. However, this trend gradually reversed over time with CPDs becoming more prominent in black than albino melanocytes at 48 h. These results show that in the absence of epidermal pigmentation, melanocytic melanin limits the tumorigenic effects of acute UV exposure but fails to protect melanocytes from UVB-induced mutagenesis. |
DOI | 10.1111/pcmr.13070 |
Alternate Journal | Pigment Cell Melanoma Res |
PubMed ID | 36148789 |
PubMed Central ID | PMC10092168 |
Grant List | P30 CA016058 / CA / NCI NIH HHS / United States R01 AR077664 / AR / NIAMS NIH HHS / United States R01 CA237213 / CA / NCI NIH HHS / United States |