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Determination of the action spectrum of UVR-induced mitochondrial DNA damage in human skin cells

Lookup NU author(s): Dr Jennifer Latimer, Dr James Lloyd, Emeritus Professor Brian Diffey, Professor Mark Birch-Machin

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

Biological responses of human skin to ultraviolet radiation (UVR) including cancer and ageing are largely wavelength-dependent as shown by the action spectra of UVR-induced erythema and nuclear DNA (nDNA) damage. A molecular dosimeter of UVR exposure is therefore required. While mitochondrial DNA (mtDNA) damage has been shown to be a reliable and sensitive biomarker of UVR exposure in human skin, its wavelength dependency is unknown. The current study solves this problem by determining the action spectrum of UVR-induced mtDNA damage in human skin. Human neonatal dermal fibroblasts and primary human adult keratinocyte cells were irradiated with increasing doses of UVR. Dose-response curves of mtDNA damage were produced for each of the UVR sources and cell types and an action spectrum for each cell type was determined by mathematical induction. Similarities between these mtDNA damage action spectra and previously determined nDNA damage were observed, with the most detrimental effects occurring over the shorter UVR wavelengths. Notably, a statistically significant (P<0.0001) greater sensitivity to mtDNA damage was observed in dermal fibroblasts compared to keratinocytes at wavelengths >300 nm, possibly indicating a wider picture of depth-dependence in sensitivity. This finding has implications for disease/photo-damage mechanisms and interventions


Publication metadata

Author(s): Latimer J, Lloyd J, Diffey B, Matts P, Birch-Machin MA

Publication type: Article

Publication status: Published

Journal: Journal of Investigative Dermatology

Year: 2015

Volume: 135

Pages: 2512-2518

Online publication date: 25/06/2015

Acceptance date: 06/05/2015

ISSN (print): 0022-202X

ISSN (electronic): 1523-1747

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/jid.2015.194

DOI: 10.1038/jid.2015.194

PubMed id: 26030182


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