title: Determination of the Action Spectrum of UVR-Induced Mitochondrial DNA Damage in Human Skin Cells.
abstract: 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.
authors.affiliation: Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK; Procter and Gamble Greater London Innovation Centre, Surrey, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Latimer
authors.affiliation: Regional Medical Physics Department, Newcastle Hospitals, Newcastle, UK.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lloyd
authors.affiliation: Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Diffey
authors.affiliation: Procter and Gamble Greater London Innovation Centre, Surrey, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Matts
authors.affiliation: Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK. Electronic address: mark.birch-machin@ncl.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birch-Machin
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D015595:Skin Aging / Q000235:genetics / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial