The skin from rats of differing age was used to quantify variations in the cell kinetics of the epidermis and the follicular epithelium of different body sites. Four parameters were assessed, namely the basal cell density (BCD), the labelling index (LI), the duration of DNA synthesis (ts) and the basal cell turnover time (tT). The BCDs of the epidermis of the dorsum and the upper surface of the foot were similar in rats of 7, 14 and 52 weeks of age, but there was an indication of a progressive decline with increasing age in the BCD of the epidermis of the ear and tail. There were no age‐related changes in the length of ts in any of the four body regions. The rate of cell proliferation, as indicated by the values of the LI and tT, was relatively rapid in the epidermis of the dorsum, foot and tail of rats aged 7 weeks (LI > 12%; tT < 80 h). In rats aged 14 weeks this rate of proliferation was maintaned in the epidermis of the dorsum. However, in the foot and tail the rate of cell proliferation was decreased (LI < 10%; tT > 85 h). A fall in the rate of proliferation of the epidermis of the dorsum was only seen in 52‐week‐old animals. In these animals the rates of proliferation in the foot and tail were similar to those at the age of 14 weeks. In the epidermis of the ear there was no appreciable change in the rate of cell proliferation with age. The values of the cell kinetic parameters varied in the different body sites. For example, in 52‐week‐old animals values for tT were relatively short in the epidermis of the tail and foot and appreciably longer in the epidermis of the dorsum and ear. Considered overall, values for the cell kinetic parameters of the epidermis were comparable with those for the follicular epithelium. The only major differences between the epidermis and the follicular epithelium were in the upper surface of the foot at 7 weeks of age, and in the tail at 7 and 14 weeks of age, where the LI was higher and the tT shorter in the epidermis than in the follicular epithelium. The relevance of the observed age‐ and body‐site‐related variations in the cell kinetics of the epidermis are discussed in relation to previously described differential changes in the radiosensitivity of the skin in this strain of rat.

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.

SUMMARY Examination of autolysed control mouse small intestine using scanning electron microscopy has revealed details of the connective tissue components of the mucosa. The cores of the villi are seen collapsed across the intervillous basin. Crypts of Lieberkuhn are seen as tubular channels stretching down from the intervillous basin. Sometimes the crypts are split in two by a connective tissue septum. The mouths of the crypts of Lieberkuhn are, in general, arranged in double rows between the single rows of villi. The ratio of number of crypts to numbers of villi was calculated as 5.01:1. This is close to the figure of 4.53:1, as quoted by Smith & Jarvis (1980) who used differential interference contrast microscopy to investigate the crypt to villus ratio. After radiation, the severe drop in the number of crypt mouths can be clearly seen by the combination of autolysis and scanning electron microscopy: the rows of crypt mouths between the villi have been lost, and many crypt mouths have been occluded by stromal tissue. The arrangement of the crypt mouths and the observation of mucosal abnormalities after irradiation have led to the postulation that cells leaving the crypt mouths move in a spiral manner towards and then up the villous surface: this postulated movement might imply an asymmetry in some properties of enterocytes. The use of scanning electron microscopy in conjugation with autolysis and irradiation has thus forced a critical re‐examination of the relationships between crypts and villi.

SUMMARY Scanning electron microscopy of the small intestine of the mouse 5 days after X‐ or neutron irradiation has revealed the formation of giant cells on the villus surface. Correlative light microscopy and transmission electron microscopy have shown that these giant cells are syncytial in nature. Characteristic features of lipid inclusions and apical microvilli suggest that these syncytia are giant enterocytes. It has also been shown that these giant cells are in contact with the connective tissue core of the villus and have a close contact with the normal enterocytes, thus maintaining mucosal integrity. It is postulated that radiation damage has caused incomplete separation during mitosis and that attempted division occurs outside the crypts of Lieberkuhn.