Some observations on radiation damage in epithelial cells of the mouse intestine
The epithelium lining the small intestine is the seat of severe and potentially lethal radiation damage. The evolution of the pathological changes indicate that the critical primary disturbance is one of cell proliferation (1).The intestinal epithelium is a renewal tissue (2). Cells are born in the crypts and mature before emerging from the mouths of the crypts; during their functional life, they migrate from the base to the tip of the villi (3). The development of tritiated thymidine as a specific label for DNA, together with high resolution autoradiography, have made possible a rather detailed study of the kinetics of cell proliferation and movements in the normal animal (4, 5) and after irradiation (6). Briefly, the events in the lower ileum of the mouse following whole body irradiation with a large dose (3 000 rad) are as follows: mitosis and DNA synthesis disappear rapidly. During the following ¾ days, ½ to 2/3 of the crypt cells disappear through cell death or through emigration onto the villi following precocious maturation [normally, cells mature only at a certain stage following mitosis (5)]. At the end of this period, the lower one-fourth of the villi is covered with cells having thus abnormally matured. During the following day, DNA synthesis is taken up again in the crypts, and no or few cells emigrate; at the same time, sloughing off of cells from the tip of the villi proceeds, and the villi shorten. Beginning about 13/4 days after irradiation, the remaining crypt cells begin to move out onto the villi, leaving the crypts empty except for Paneth cells. No mitosis intervenes between DNA synthesis and maturation, and the resulting cells are very large and misshapen. After they, too, have been desquamated, the villi collapse and the intestine is denuded (1). The Paneth cells show some early changes (6) but seem to recover and succumb only on the fourth day.
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