Scanning electron microscopy of mouse intestinal mucosa after cobalt 60 and D-T neutron irradiation

The stem-cell population of the intestinal crypt is an important model system in experimental radiobiology. Standardized techniques have been developed to allow quantitation of the response of crypt cells to radiation injury following doses of 0-2 krad of D-T neutrons or 60Co gamma rays. These techniques rely on the identification of regenerating crypt cells three-and-a-half days after irradiation. The results are expressed as the number of regenerating crypts per circumference of small intestine, as determined by conventional histological examination; the more profound the injury, the smaller the crypt count. The practical relevance of crypt-counting techniques to clinical radiotherapy is limited by their relative insensitivity; the dose levels commonly used in fractionated radiotherapy produce no detectable response. Scanning electron microscopy of the mucosal surface provides a more sensitive measure of radiation injury. The earliest detectable changes occur at the level of 300 rad of gamma radiation, well below the threshold of the crypt-counting technique. At around 1,000 rad, where the first drop in crypt counts occurs, there are well-marked morphological changes which become more severe with increasing dose levels. Some differences have been observed between the morphological effects of gamma and neutron irradiation at points of radiobiological equivalence in terms of crypt counts (using an RBE value of about 2). The changes observed may reflect more than the disruption of epithelial cell kinetics. Mucosal morphology is the total expression of many different biological parameters of which the regenerative ability of the crypt cells is only one. The surface microanatomy of the gut may be the most sensitive indicator of radiation injury which is conveniently available for study.