Tissue kinetics in mouse tongue mucosa during daily fractionated radiotherapy

The purpose of the present investigation was to quantify cell flux between the distinct layers of the epithelial lining of the ventral surface of mouse tongue during daily fractionated radiotherapy. A fraction of DNA-synthesizing cells in control epithelium, or at various days through a course of daily fractionated radiotherapy with 3 or 4 Gy per day, was labelled with [H-3]dT or BrdUrd, respectively. The labelling indices (LI) in the different epithelial layers were defined histologically after autoradiography, or immunohistochemistry, at intervals between 1 and 10 days after label administration. In tongue epithelium of untreated mice, the minimum residence time of cells in the germinal layer is 2-3 days. Migration through the functional layers requires an additional 2-3 days before labelled cells are observed in the most superficial layer of nucleated cells. A plateau in LI is observed for several days post-labelling in control epithelium, indicating an equilibrium between loss and proliferation of labelled cells. During fractionated radiotherapy, the minimum time from division to occurrence of labelled cells in the stratum lucidum is less than 2 days, and hence significantly shorter than in control epithelium. In contrast to untreated epithelium, no plateau in the germinal layer LI is seen, indicating that frequently both labelled daughters from dividing labelled cells are being lost from this compartment. In conclusion, the present data support a recently described model of radiation-induced accelerated repopulation in squamous epithelia, which postulates that the majority of damaged cells undergoes abortive' divisions resulting in two differentiating daughters.