The Temporal and Spatial Changes in Cell Proliferation within the Irradiated Crypts of the Murine Small Intestine

Summary

The detailed temporal and spatial changes in the labelling index in crypts of the small intestine of the mouse have been analysed after 8·0 Gy γ-irradiation. The labelling index was determined for each cell position in the crypts at 34 different times between 3 and 192 h after irradiation. The changes between consecutive time points have been analysed to determine the details of the crypt shrinkage and crypt repopulation phenomena. The following points can be made: (1) There is a dramatic reduction in the overall labelling of the crypt which begins within 3 h and is at its minimum by 15 h postirradiation. Most of this shrinkage can be attributed to continued near-normal emigration of cells from the crypt to the villus while mitosis is reduced or absent, and a possibly premature maturation within the transit population. (2) The labelling index never falls below 34 per cent of control, i.e. many labelled cells persist and continue to replicate their DNA at all times postirradiation. (3) Repopulation begins in the lower regions of the crypt. The first changes are an increase in labelling at cell positions 3–8 that begins at 3 h and reaches a peak at 12 h. There is a second increase in proliferation at the crypt base that begins at about 15 h and reaches a peak at 22–32 h postirradiation. There is a third peak which begins at about 46 h and reaches a peak at 60–70 h. (4) There is a reduction in proliferation at the crypt base that begins at about 72 h postirradiation. (5) The mid and upper crypt population shrinks initially to reach a minimum at about 15 h, after which there is a steady increase to reach a peak at about 72 h. The labelling spreads into the crypt-villus boundary area beginning at about 32 h. There is a reduction of proliferative activity in the mid-crypt region that begins at about 72 h. (6) There is a dramatic overshoot in overall labelling index at 72 h, which involves mainly the upper crypt. This does not revert to normal levels within the 192 h time scale of the present experiments. There is a mild overshoot in labelling at the crypt base at 48–78 h with a return to normal levels thereafter. It can be concluded that early changes in the crypt, probably the small levels of acute cell death, result in an early stimulation of stem cell proliferation, the signals for which must be local in action. These in turn lead to further rounds of stem cell proliferation and transit cell repopulation.