Impaired skin barrier due to sebaceous gland atrophy 2 in the latent stage of radiation - induced skin injury : 3 application of non - invasive diagnostic methods 4 5

1 Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea 8 Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea 9 2 Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 10 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea 11 *Correspondence: E-mail: [email protected]; Tel.: +82-2-3399-5873 and E-mail: [email protected]; Tel.: 12 +82-2-3399-5803 13 14 Abstract: Radiation-induced skin injury can be a serious cutaneous damage and have specific 15 characteristics. Asymptomatic periods are classified as the latent stage. The skin barrier plays a 16 critical role in the modulation of skin permeability and hydration and protects the body against a 17 harsh external environment. However, an analysis on the skin barrier dysfunction against radiation 18 exposure in the latent stage has not been conducted. Thus, we investigated whether skin barrier is 19 impaired by irradiation in the latent stage and aimed to identify the molecules involved in skin barrier 20 dysfunction. We analyzed skin barrier function and its components in SKH-1 mice that received 20 21 and 40 Gy local irradiation. Increased transepidermal water loss and skin pH were observed in the 22 latent stage of the irradiated skin. Skin barrier components, such as structural proteins and lipid 23 synthesis enzymes in keratinocyte, increased in the irradiated group. Interestingly, we noted 24 sebaceous gland atrophy and increased serine protease and inflammatory cytokines in the irradiated 25 skin during the latent period. This finding indicates that the main factor of skin barrier dysfunction 26 in the latent stage of radiation-induced skin injury is sebaceous gland deficiency, which could be an 27 intervention target for skin barrier impairment. 28 29