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

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...

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Published in:	Journal of radiation research Vol. 58; no. 5; pp. 636 - 646
Main Authors:	McCart, Elizabeth A, Thangapazham, Rajesh L, Lombardini, Eric D, Mog, Steven R, Panganiban, Ronald Allan M, Dickson, Kelley M, Mansur, Rihab A, Nagy, Vitaly, Kim, Sung-Yop, Selwyn, Reed, Landauer, Michael R, Darling, Thomas N, Day, Regina M
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-09-2017
Subjects:	Adult Stem Cells - radiation effects Aging Animals Apoptosis - radiation effects Biology Cellular Senescence - radiation effects Disease Models, Animal Dose-Response Relationship, Radiation Female Fibrosis Hair Follicle - pathology Hair Follicle - radiation effects Keratinocytes - pathology Keratinocytes - radiation effects Mice, Inbred C57BL Organ Specificity - radiation effects Radiation Injuries - pathology Skin - pathology Skin - radiation effects Skin Aging - radiation effects Ulcer - pathology hair follicle stem cells dermatitis p21/waf1 accelerated senescence ionizing radiation
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0449-3060 1349-9157
DOI:	10.1093/jrr/rrx008