Establishment and characterization of a radiation‐induced dermatitis rat model

Abstract

Radiation‐induced dermatitis is a common and serious side effect after radiotherapy. Current clinical treatments cannot efficiently or fully prevent the occurrence of post‐irradiation dermatitis, which remains a significant clinical problem. Resolving this challenge requires gaining a better understanding of the precise pathophysiology, which in turn requires establishment of a suitable animal model that mimics the clinical condition, and can also be used to investigate the mechanism and explore effective treatment options. In this study, a single dose of 90 Gy irradiation to rats resulted in ulceration, dermal thickening, inflammation, hair follicle loss, and sebaceous glands loss, indicating successful establishment of the model. Few hair follicle cells migrated to form epidermal cells, and both the severity of skin fibrosis and hydroxyproline levels increased with time post‐irradiation. Radiation damaged the mitochondria and induced both apoptosis and autophagy of the skin cells. Therefore, irradiation of 90 Gy can be used to successfully establish a rat model of radiation‐induced dermatitis. This model will be helpful for developing new treatments and gaining a better understanding of the pathological mechanism of radiation‐induced dermatitis. Specifically, our results suggest autophagy regulation as a potentially effective therapeutic target.

Radiation-irritated skin and hyperpigmentation may impact the quality of life of breast cancer patients after whole breast radiotherapy

“…“Radiation-irritated skin” is a brand-new concept of the sequelae of radiation therapy that no one reported in the past. According to previous studies, [ 6 , 12 , 14 , 15 ] we concluded that the possible pathological mechanism of “Radiation-irritated skin” may consist of changes such as thickening of epidermis, hyperkeratosis, and atrophy of sweat gland and sebaceous gland.(Fig. 3 ) In this study, 46.3% of breast cancer patients after whole breast radiotherapy may develop “radiation-irritated skin”.…”

“…Similarly, skin accessory tissues such as sweat glands, sebaceous glands, and hair follicles are also sensitive to radiation. In rat model, irradiation to the skin will result in irreversible pathological changes such as sebaceous glands loss, hair follicles loss, increased epidermal thickness, and skin fibrosis [ 6 , 15 ]. We found skin dryness and hotness in the radiation field impacted the quality of life of breast survivors after radiotherapy and led to inferiority or depression.…”

“…Clinical observations and animal models indicate that the skin dryness and absent sweating is due to the pathophysiological changes of the sweat glands and sebaceous glands caused by radiation. In addition, increased epidermis thickness, keratinization, and subcutaneous collagen fiber loss were also reported after radiation exposure [ 12 , 15 ].…”

Initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin

“…In spite of this, results corroborate what has been described for the skin that covers the most regions of the body [28,29], related with drastic but temporary atrophy of sebaceous glands and hair follicles. We found that between day 4 and day 14, these epidermal components disappeared.…”

Mitochondrial dysfunction in fibrotic diseases

“…Radiation‐induced dermatitis can cause skin fibrosis, and radiation also damages mitochondria 108 . Radiation-induced subcutaneous fibrosis can also be associated with genetic variation of thioredoxin reductase 2 (Txnrd2), a mitochondrial enzyme involved in removal of ROS 109 .…”