Abstract
BackgroundRadiation technology focuses on delivering the radiation as precisely as possible to the tumor, nonetheless both acute and long-term damage to surrounding normal tissue may develop. Injuries to the surrounding normal tissue after radiotherapy of head and neck cancer are difficult to manage. An animal model is needed to elucidate good treatment modalities. The aim of this study was to establish a rat model where a certain radiation dose gives reproducible tissue reactions in the mandibular area corresponding to injuries obtained in humans.MethodThe left mandible of male Sprague Dawley rats was irradiated by external radiotherapy (single fraction 15 Gy, total dose 75 Gy) every second week five times. Endpoint was six weeks after last radiation treatment, and the test group was compared to non-irradiated controls. Morphological alterations of the soft tissues, bone and tooth formation, as well as alterations of salivation, vascularity and collagen content were assessed. An unpaired, non-parametric Mann–Whitney test was used to compare the statistical differences between the groups.ResultsAnalysis of the soft tissues and mandible within the radiation field revealed severe unilateral alopecia and dermatitis of the skin, extensive inflammation of the submandibular gland with loss of serous secretory cells, hyperkeratinization and dense connective fiber bundles of the gingival tissue, and disturbed tooth development with necrosis of the pulp. Production of saliva and the vascularity of the soft tissues were significantly reduced. Furthermore, the collagen fibril diameter was larger and the collagen network denser compared to non-irradiated control rats.ConclusionWe have established an animal model of radiation injury demonstrating physiological and histological changes corresponding to human radiation injuries, which can be used for future therapeutic evaluations.
Highlights
Radiation technology focuses on delivering the radiation as precisely as possible to the tumor, both acute and long-term damage to surrounding normal tissue may develop
We have established an animal model of radiation injury demonstrating physiological and histological changes corresponding to human radiation injuries, which can be used for future therapeutic evaluations
To determine the impact of 5 × 15 Gy radiotherapy targeted to the left mandible parameters such as histology, salivation, vascular density and collagen content were analyzed in the skin, muscle, submandibular gland and mandible of the radiation field
Summary
Radiation technology focuses on delivering the radiation as precisely as possible to the tumor, both acute and long-term damage to surrounding normal tissue may develop. Injuries to the surrounding normal tissue after radiotherapy of head and neck cancer are difficult to manage. Head and neck cancer (HNC) is a heterogeneous group of neoplasms that share a common anatomic origin. These tumors develop within the mucosa that lines the upper aerodigestive tract (squamous-cell carcinomas) or the different glands in this region (adenocarcinomas). Normal cells have a greater capacity than tumor cells to repair the radiation damage, especially at low doses [5]. This makes fractionated radiotherapy efficient in sparing normal
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