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Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin

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 r...

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Autores principales: Weiss, Tirzah J., Crawford, Emma R., Posada, Valentina, Rahman, Hafeez, Liu, Tong, Murphy, Brandon M., Arnold, Tiffany E., Gray, Shannon, Hu, Zhexuan, Hennessey, Rebecca C., Yu, Lianbo, D'Orazio, John A., Burd, Craig J., Zippin, Jonathan H., Grossman, Douglas, Burd, Christin E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092168/
https://www.ncbi.nlm.nih.gov/pubmed/36148789
http://dx.doi.org/10.1111/pcmr.13070
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author Weiss, Tirzah J.
Crawford, Emma R.
Posada, Valentina
Rahman, Hafeez
Liu, Tong
Murphy, Brandon M.
Arnold, Tiffany E.
Gray, Shannon
Hu, Zhexuan
Hennessey, Rebecca C.
Yu, Lianbo
D'Orazio, John A.
Burd, Craig J.
Zippin, Jonathan H.
Grossman, Douglas
Burd, Christin E.
author_facet Weiss, Tirzah J.
Crawford, Emma R.
Posada, Valentina
Rahman, Hafeez
Liu, Tong
Murphy, Brandon M.
Arnold, Tiffany E.
Gray, Shannon
Hu, Zhexuan
Hennessey, Rebecca C.
Yu, Lianbo
D'Orazio, John A.
Burd, Craig J.
Zippin, Jonathan H.
Grossman, Douglas
Burd, Christin E.
author_sort Weiss, Tirzah J.
collection PubMed
description 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.
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spelling pubmed-100921682023-04-13 Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin Weiss, Tirzah J. Crawford, Emma R. Posada, Valentina Rahman, Hafeez Liu, Tong Murphy, Brandon M. Arnold, Tiffany E. Gray, Shannon Hu, Zhexuan Hennessey, Rebecca C. Yu, Lianbo D'Orazio, John A. Burd, Craig J. Zippin, Jonathan H. Grossman, Douglas Burd, Christin E. Pigment Cell Melanoma Res Original Articles 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. John Wiley and Sons Inc. 2022-10-09 2023-01 /pmc/articles/PMC10092168/ /pubmed/36148789 http://dx.doi.org/10.1111/pcmr.13070 Text en © 2022 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Weiss, Tirzah J.
Crawford, Emma R.
Posada, Valentina
Rahman, Hafeez
Liu, Tong
Murphy, Brandon M.
Arnold, Tiffany E.
Gray, Shannon
Hu, Zhexuan
Hennessey, Rebecca C.
Yu, Lianbo
D'Orazio, John A.
Burd, Craig J.
Zippin, Jonathan H.
Grossman, Douglas
Burd, Christin E.
Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin
title Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin
title_full Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin
title_fullStr Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin
title_full_unstemmed Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin
title_short Cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin
title_sort cell‐intrinsic melanin fails to protect melanocytes from ultraviolet‐mutagenesis in the absence of epidermal melanin
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092168/
https://www.ncbi.nlm.nih.gov/pubmed/36148789
http://dx.doi.org/10.1111/pcmr.13070
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