title: An Immunohistochemical Study on the Role of Oxidative and Nitrosative Stress in Irradiated Skin.
abstract: OBJECTIVE
  The effects of ionizing radiation through the generation of free radicals, reactive aldehydes, and other oxidative and nitrosative by-products account for skin injuries as side effects of radiation therapy (RT). This study aims to identify cellular pathways in oxidative and nitrosative stress in irradiated skin using well-established marker proteins in an immunohistochemical analysis.
  
  
  METHODS
  Tissue specimens of 51 patients were obtained during operative access to the neck. Twenty patients (39.2%) received RT prior to the surgical intervention. Immunohistochemical analysis of stable degradation products of reactive oxygen and nitrogen species (RONS), 3-nitrotyrosine, 8-isoprostane, phosphorylated AKT (p-AKT), and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed in specimens which were exposed to RT and those without a history of RT.
  
  
  RESULTS
  Immunohistochemical staining showed a significantly increased expression of nitrotyrosine in superficial and basal epidermal regions of interest (ROI), p-AKT in all epidermal ROI, and p-ERK in all the investigated epidermal and dermal ROI, as well as in an overall analysis. No significance could be detected in immunostaining against isoprostane.
  
  
  CONCLUSIONS
  This study summarizes the influence of RONS in RT. Moreover, a detailed histological analysis was able to identify epidermal ROI as a main starting point of RONS in irradiated skin. Even though the role of RONS in high-dose therapeutic radiation remains a subject for further research, these data underlines the crucial role of RONS in high-dose radiation.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Technical University of Munich (TUM), Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Koerdt
authors.forename: Nadine
authors.initials: N
authors.lastname: Tanner
authors.forename: Niklas
authors.initials: N
authors.lastname: Rommel
authors.forename: Nils H
authors.initials: NH
authors.lastname: Rohleder
authors.forename: Mechthild
authors.initials: M
authors.lastname: Stoeckelhuber
authors.forename: Klaus-Dietrich
authors.initials: KD
authors.lastname: Wolff
authors.forename: Marco R
authors.initials: MR
authors.lastname: Kesting
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015538:Nitrosation; D018384:Oxidative Stress; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D055815:Young Adult
chemical_list: C075750:8-epi-prostaglandin F2alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D015237:Dinoprost; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases