Three A's of repopulation during fractionated irradiation of squamous epithelia: Asymmetry loss, acceleration of stem-cell divisions and abortive divisions

Purpose: To analyse the time-course and efficacy of repopulation in squamous epithelia, and to describe possible mechanisms of this regeneration response. Material and methods: Experimental and clinical studies of repopulation in squamous epithelia have been reviewed to outline general features of repopulation during fractionated radiotherapy. Results: Repopulation processes result in a relative increase in re-irradiation tolerance, which can be quantified as the dose equivalent compensated. Conclusions: If the stem-cell concept is accepted, changes in residual tissue tolerance must be based on net production of stem cells. For this, normal asymmetrical stem-cell divisions that render equal numbers of stem cells and differentiating daughters, must turn into symmetrical divisions with the production of two stem cells. Furthermore, the rate of change in residual tolerance indicates that the stem-cell proliferation rate is increased. In addition to these changes in the stem-cell proliferation pattern, a limited number of divisions by sterilized cells contributes to overall cell production and maintenance of tissue function. A valid model of repopulation in squamous epithelia hence must be based on three distinct mechanisms summarized as the three As: Asymmetry loss, Acceleration of stem-cell divisions, and Abortive divisions.