REPOPULATION RESPONSE OF MOUSE ORAL-MUCOSA DURING UNCONVENTIONAL RADIOTHERAPY PROTOCOLS

Repopulation in mouse tongue epithelium was determined during unconven tional fractionation schedules, i.e., hyperfractionation (2 x 1.5 and 2 x 1.75 Gy/day) and accelerated treatment (2 x 3 Gy/day). The residua l tolerance of the epithelium at defined days of the fractionated trea tment was tested by graded single test doses (top-up design). The dose required to induce complete epithelial denudation in 50% of the anima ls (ED50) was used to calculate the number of fractions repopulated du ring the preceding treatment. After the first week of hyperfractionati on, tolerance was reduced compared to untreated epithelium However, su bsequently no further change was observed, indicating complete compens ation of the weekly dose with all doses per fraction used. Epithelial cell density, defined by histological examination in additional experi ments, in all fractionation arms decreased similarly by similar to 40% during the first week and remained constant at 60-80% in the subseque nt 2 weeks. During accelerated fractionation, the residual mucosal tol erance decreased continuously with treatment time and resulted in epit helial denudation after 12 fractions. However, a substantial repopulat ion effect was observed, compensating 1.5 fractions by day 2, and 5 fr actions by day 5, respectively. After cessation of the therapy the rep opulation rate clearly decelerated to compensate a dose equivalent to about 0.5 fractions per day. Cell density decreased linearly during th e treatment with 5, 10 or 12 fractions at a rate close to normal cell loss. Marked cell production, dependent on the total fractionated dose , was seen from one day after the last fraction in each experimental a rm. These results indicate that maximum stem cell repopulation occurs predominantly during treatment, while major production of differentiat ing cells takes place in treatment splits.