TISSUE KINETICS IN MOUSE TONGUE MUCOSA DURING DAILY FRACTIONATED RADIOTHERAPY

The purpose of the present investigation was to quantify cell flux bet ween the distinct layers of the epithelial lining of the ventral surfa ce of mouse tongue during daily fractionated radiotherapy. A fraction of DNA-synthesizing cells in control epithelium, or at various days th rough a course of daily fractionated radiotherapy with 3 or 4 Gy per d ay, was labelled with [H-3]dT or BrdUrd, respectively. The labelling i ndices (LI) in the different epithelial layers were defined histologic ally after autoradiography, or immunohistochemistry, at intervals betw een 1 and 10 days after label administration. In tongue epithelium of untreated mice, the minimum residence time of cells in the germinal la yer is 2-3 days. Migration through the functional layers requires an a dditional 2-3 days before labelled cells are observed in the most supe rficial layer of nucleated cells. A plateau in LI is observed for seve ral days post-labelling in control epithelium, indicating an equilibri um between loss and proliferation of labelled cells. During fractionat ed radiotherapy, the minimum time from division to occurrence of label led cells in the stratum lucidum is less than 2 days, and hence signif icantly shorter than in control epithelium. In contrast to untreated e pithelium, no plateau in the germinal layer LI is seen, indicating tha t frequently both labelled daughters from dividing labelled cells are being lost from this compartment. In conclusion, the present data supp ort a recently described model of radiation-induced accelerated repopu lation in squamous epithelia, which postulates that the majority of da maged cells undergoes abortive' divisions resulting in two differentia ting daughters.