An Immunohistochemical Panel to Assess Ultraviolet Radiation-Associated Oxidative Skin Injury
May 2014 | Volume 13 | Issue 5 | Original Article | 574 | Copyright © May 2014
Andrew Mamalis*,a,b Natallia Fiadorchanka MD*,c Lauren Adams MD,b Melissa Serravallo MD,c
Edward Heilman MD,c Daniel Siegel MD MS,c Neil Brody MD PhD,c and Jared Jagdeo MD MSa,b,c
aDepartment of Dermatology, University of California Davis, Sacramento, CA
bDermatology Service, Sacramento VA Medical Center, Mather, CA
cDepartment of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY
*These authors contributed equally to the preparation of this manuscript.
Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years (DALYs), and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation. J Drugs Dermatol.
Ultraviolet (UV) radiation, a form of ionizing radiation, results in approximately 1.5 million disability-adjusted life years (DALYs) and is associated with greater than 60,000 deaths annually worldwide attributed to melanoma and other skin cancers.1 There are no standardized biomarker panels to assess UV-radiation oxidative stress injury patterns in skin. Unless assessing erythema after UV exposure, it is difficult to clinically determine the efficacy of UV-protective agents.2-6 Therefore, developing a biomarker panel to evaluate UV radiation oxidative damage would facilitate rapid evaluation of skin injury due to UV radiation and enable the development and evaluation of novel oxidation-protective agents, such as sunscreens and topical antioxidants, to treat or prevent UV radiation-induced oxidation resulting in a decrease in lost years of healthy life, DALYs, and annual deaths that are attributed to UV radiation.7
UV and other forms of ionizing radiation cause skin injury through the generation of free radicals, reactive aldehydes and other oxidative byproducts.8 These free radicals and oxidative byproducts damage DNA, lipids, and proteins.9-11 Oxidative damage to DNA, lipids, and proteins disrupts normal cellular functions and is thought to play a major role in the pathogenesis of skin aging, cancer, and inflammatory skin diseases through the generation of gene mutations and post-translational modifications of essential cancer-related proteins.8 These mutations and modifications alter the cellular pathways involved in cell growth, apoptosis, DNA repair, cell cycle regulation, and gene expression leading to either inactivation of tumor-suppressor genes or enhancement of proto-oncogenes.8,12
Our results demonstrate that UV radiation-induced oxidative damage can be evaluated by an immunohistochemical panel that includes 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage (Table 1). Together these markers serve as a comprehensive panel to evaluate UV radiation damage to critical skin components. To demonstrate this panel’s utility, we conducted a study to characterize and quantify the aforementioned oxidative damage byproducts in chronic solar UV-exposed human skin compared with UV-protected human skin.
MATERIALS AND METHODS
This study was approved by Western Institutional Review Board. Biopsy specimens were obtained under an IRB-approved waiver of consent due to use of de-identified samples of residual tissue not needed for clinical purposes.