RADIOBIOLOGICAL MODELS OF NORMAL TISSUE-REACTIONS

Purpose: The present review summarizes radiobiological models of norma l tissue responses to radiation and their consequences for potential t herapeutic interventions. Material and Methods: Common radiobiological principles and pathogenetic models can be established for classes of tissues. These models may support the development of general modalitie s, both therapeutic and supportive, for the modulation of these respon ses. Results: The stem cell concept, based on studies in standard tiss ue culture, describes the clonogenic survival after radiation treatmen t. The factors affecting cell survival are summarized as the 4 Rs of r adiotherapy. Based on the stem cell concept, the reactions of normal t issue to ionising radiation were considered a consequence exclusively of the proliferative sterilisation of cells of a given target cell pop ulation. Once stem cells are inactivated, responses develop in a passi ve manner. However, recent studies into the pathogenesis of radiation tissue injury have clearly shown that numerous postirradiation events occur during the symptom-free latent time in irradiated cells and tiss ues, which modulate the manifestation of damage. These are summarized by models of tissue radiation pathology. Conclusions: Cellular radiobi ology and the tissue models based on the stem cell concept assume that exclusively the sterilisation of target cells is the radiation effect which results in both acute and late tissue responses. As a consequen ce, the radiation sensitivity can only be modulated by modification of radiobiological parameters at the time of irradiation, while at later time points only symptomatic treatment can be applied. Tissue radiati on pathology, in contrast, allows for post-irradiation modification of the manifestation of radiation sequelae in tissues.