Determination of the Action Spectrum of UVR-Induced Mitochondrial DNA Damage in Human Skin Cells
Open accessAbstract
Biological responses of human skin to UVR including cancer and aging 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. Although 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 with keratinocytes at wavelengths >300 nm, possibly indicating a wider picture of depth dependence in sensitivity. This finding has implications for disease/photodamage mechanisms and interventions.
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Mitochondrial DNA is more vulnerable to damage at UVR wavelengths >320 nm compared with nuclear DNA.
“A recent study looking at the action spectrum of UVR-induced mitochondrial damage showed that mitochondrial DNA is more vulnerable to damage at UVR wavelengths >320 nm when compared with nuclear DNA [25].”
From Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin (2017) · cites this paper as [25]
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Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin
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Self-citation
- Authors
- Latimer, J. A., Lloyd, J. J., Diffey, B. L., Matts, P. J., & Birch-Machin, M. A.
- Affiliations
- Procter & Gamble (United Kingdom) (GB)
- Newcastle University (GB)
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 135
- Issue
- 10
- Pages
- 2512-2518
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1915186499
- Cited by
- 15
- References
- 23
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc)
- Funders
- Engineering and Physical Sciences Research Council
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- ultraviolet radiation, mitochondrial DNA damage, action spectrum, wavelength dependence, human skin, dermal fibroblasts, keratinocytes, photodamage
- MeSH terms
- Adult, Aged, Cells, Cultured, DNA Damage, DNA, Mitochondrial, Dose-Response Relationship, Radiation, Fibroblasts, Humans, Male, Middle Aged, Sampling Studies, Sensitivity and Specificity, Skin, Ultraviolet Rays, Skin Aging, Keratinocytes, Young Adult
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