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J Photochem Photobiol B. 2014 Mar 5;132:56-65. doi: 10.1016/j.jphotobiol.2014.01.019. Epub 2014 Feb 12.

Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.

Author information

1
The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Biomedical Engineering, College of Engineering, University of Arizona, Tucson, AZ, USA.
2
The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Medicine, University of Arizona, Tucson, AZ, USA.
3
The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA.
4
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
5
Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ, USA.
6
The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA. Electronic address: wondrak@pharmacy.arizona.edu.

Abstract

Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than threefold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored.

KEYWORDS:

DHP-lysine; Lipid peroxidation; Malondialdehyde; Nonmelanoma skin cancer; Photocarcinogenesis; Photodamage

PMID:
24584085
PMCID:
PMC3973651
DOI:
10.1016/j.jphotobiol.2014.01.019
[Indexed for MEDLINE]
Free PMC Article

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