Review article: Effects of radiation on the cell proliferation kinetics of epithelial tissues—therapeutic implications

The cell kinetic responses of the epithelia of the skin, oral mucosa and intestine to photon irradiation are reviewed. One of the fundamental assumptions made in the development of mathematical models, used to predict the acute response of normal tissues to changes in fractionation protocols, is "equal effect per fraction". There is now accumulating cell kinetic data to indicate that this assumption is unlikely to be valid. The implications of these findings are discussed. The reaction of acutely responding epithelial tissues to ionizing radiation has significant implications for the radiation oncologist. Epithelia are important dose limiting normal tissues, in that, damage induced by the radiation treatment has to be balanced against the probability of achieving local tumour control. The rate of development of radiation damage in epithelial tissues is intimately linked to their cell population kinetics. It is generally assumed in the use of fractionated radiotherapy that if the interfraction interval is long enough to enable the complete repair of sublethal damage, and the total treatment time is shorter than the time at which repopulation commences, then each radiation fraction has a similar biological effect. In mathematical models developed to delineate the response of normal tissues to fractionated irradiation, it is assumed that the target stem cells have a similar radiation sensitivity throughout the fractionation regime. In this review, the published data on radiation induced changes in the cell population dynamics of epithelia are discussed, in terms of the concept of "equal effect per fraction". Three representative types of epithelia tissue are included, namely the epidermis, the intestinal epithelium and the oral mucosa. These are the epithelia that have been most extensively investigated, with regard to their cell kinetic response to ionizing radiation. Radiation sensitivity and the cell cycle Variation in the radiosensitivity of cells in different phases of the cell cycle was first demonstrated in vitro in the 1960s [1,2]. Cells that are in the mitotic and late G2 phases of the cell cycle are generally the most sensitive to radiation, with cells in the late S phase being the most resistant. Cells in the early S phase, and also in the Gx phase, tend to have an intermediate radiosensitivity. There have been few reports on cell cycle phase related