Biological Basis for Skin and Mucosal Toxicity

Abstract

Both the epidermis, which is a keratinizing squamous epithelium, and the oral mucosa, which is a nonkeratinizing squamous epithelium, are characterized by rapid cell turnover. In normal squamous epithelium, cell production and cell differentiation are well organized in separate cell layers with unidirectional flow of cells from the suprabasal to the superficial cell layers. The life span of a newly formed cell in the germinative layer of the human oral mucosa until its sequestration from the mucosal surface is about 5 days; i.e. about once per week the mucosa is completely replaced by a new mucosal membrane through cell production by the stem cells and the transit cells in the germinative layer. Irradiation causes mucositis (and, in an analogous way, dermatitis) by inhibiting the cell production which is needed for this continuous replacement. For this reason, after high single doses or very accelerated irradiation, the latency to the characteristic signs of acute radiation injury is similar or only a little longer than the normal epithelial turnover time, i.e. about 1 week in oral mucosa and 2 weeks in skin. The radiation-induced inhibition of cell production causes an acute hypoplasia in the epithelium. The symptoms of acute radiation injury such as erythema and pain, however, do not arise in the hypoplastic epithelium itself but in the supporting vascular connective tissue, i.e. the submucosa and dermis, respectively, probably in response to the functional insufficiency of the hypoplastic epithelium.