REPOPULATION OF MOUSE JEJUNAL CRYPT CELLS

The regenerative response to radiation of mouse jejunal crypt cells was investigated using a three fraction experiment. The time between the second and third fraction was varied between 5 and 60 h, and the dose in each of the three fractions was different. The data show that the onset of regeneration is within 14 h of the first dose and possibly earlier. The doubling time of the clonogenic cells during repopulation is estimated to be between 5 and 10 h, with the most likely value approximately 6 to 7 h. The data also show that the time course of repopulation in an acutely responding tissue depended in a complex way on the fractionation scheme. The implications of this for radiotherapy are that simple formulas are unlikely to be accurate predictors of acute effects in altered fractionation schemes. Detailed mathematical modelling of the data is undertaken using a model which consists of a single dose survival curve, a part to incorporate the regenerative response and a part to accommodate the delayed onset of regeneration. The model is shown to give a good, although not perfect, fit to the data. A mathematical derivation is given of the expected number of crypts following the 3 dose radiation schedule. This derivation takes into account the fact that any crypt could be denuded of cells prior to the final dose and hence not repopulate, and thus the formula given is necessarily more complex than previous formulas which were based on simpler models.