Journal Article

Accelerated senescence in skin in a murine model of radiation-induced multi-organ injury

Elizabeth A McCart, Rajesh L Thangapazham, Eric D Lombardini, Steven R Mog, Ronald Allan M Panganiban, Kelley M Dickson, Rihab A Mansur, Vitaly Nagy, Sung-Yop Kim, Reed Selwyn, Michael R Landauer, Thomas N Darling and Regina M Day

in Journal of Radiation Research

Volume 58, issue 5, pages 636-646
Published in print September 2017 | ISSN: 0449-3060
Published online March 2017 | e-ISSN: 1349-9157 | DOI: https://dx.doi.org/10.1093/jrr/rrx008
Accelerated senescence in skin in a murine model of radiation-induced multi-organ injury

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  • Clinical Genetics
  • Molecular Biology and Genetics
  • Epidemiology
  • Radiology
  • Nuclear Chemistry, Photochemistry, and Radiation

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Abstract

Accidental high-dose radiation exposures can lead to multi-organ injuries, including radiation dermatitis. The types of cellular damage leading to radiation dermatitis are not completely understood. To identify the cellular mechanisms that underlie radiation-induced skin injury in vivo, we evaluated the time-course of cellular effects of radiation (14, 16 or 17 Gy X-rays; 0.5 Gy/min) in the skin of C57BL/6 mice. Irradiation of 14 Gy induced mild inflammation, observed histologically, but no visible hair loss or erythema. However, 16 or 17 Gy radiation induced dry desquamation, erythema and mild ulceration, detectable within 14 days post-irradiation. Histological evaluation revealed inflammation with mast cell infiltration within 14 days. Fibrosis occurred 80 days following 17 Gy irradiation, with collagen deposition, admixed with neutrophilic dermatitis, and necrotic debris. We found that in cultures of normal human keratinocytes, exposure to 17.9 Gy irradiation caused the upregulation of p21/waf1, a marker of senescence. Using western blot analysis of 17.9 Gy–irradiated mice skin samples, we also detected a marker of accelerated senescence (p21/waf1) 7 days post-irradiation, and a marker of cellular apoptosis (activated caspase-3) at 30 days, both preceding histological evidence of inflammatory infiltrates. Immunohistochemistry revealed reduced epithelial stem cells from hair follicles 14–30 days post-irradiation. Furthermore, p21/waf1 expression was increased in the region of the hair follicle stem cells at 14 days post 17 Gy irradiation. These data indicate that radiation induces accelerated cellular senescence in the region of the stem cell population of the skin.

Keywords: dermatitis; ionizing radiation; accelerated senescence; p21/waf1; hair follicle stem cells

Journal Article.  6543 words.  Illustrated.

Subjects: Clinical Genetics ; Molecular Biology and Genetics ; Epidemiology ; Radiology ; Nuclear Chemistry, Photochemistry, and Radiation

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