Adult male mice were given a continuous infusion of about 0.5 muCi of 3H-thymidine per gram body weight per day for periods varying from 1 to 60 days. Semithin sections of descending colon were cut from/plastic-embedded blocks and stained by a method combining silver impregnation and iron hematoxylin, by which argentaffin entero-endocrine cells and caveolated cells could be identified. From radioautographs, the labeling index of these cells was determined. One to three days after the beginning of 3H-thymidine infusion, label is observed in some of the stained entero-endocrine cells in the bottom of the crypts; the apices of these cells reach the crypt lumen and are joined to neighboring cells by terminal bars (junctional complexes). After five to seven days, labeled entero-endocrine cells are seen on the sides of the crypts, where their base stretches along the basement membrane and their apex has lost its terminal bar connections to neighboring cells. Finally, by 13 and 24 days, labeled cells are observed within the epithelium at the mucosal surface. The turnover time, which is taken to be equal to the mean time required for migration from site of origin to site of loss on the mucosal surface, has been estimated at 23.3 days. This is much longer than the 4.6 days required by the two main cell types of the epithelium -- vacuolated-columnar and mucous cells -- to travel the same route. It is likely that, after entero-endocrine cells lose their terminal bar attachment to other epithelial cells, they migrate independently and very slowly. Labeled caveolated cells are first seen in the crypt bottom one day after the beginning of 3H-thymidine infusion. By three to five days, they are on the sides of the crypts; their base is stretched along the basement membrane, but their apex retains its attachment to neighboring cells by terminal bars. By seven days, labeled caveolated cells are on the mucosal surface. Their turnover time has been assessed at 8.2 days. This is, again, longer than for the two main types to which they are bound by terminal bars throughout migration. The discrepancy is explained by the caveolated cells arising deeper in the crypts than most vacuolated-columnar and mucous cells.

Epithelial cell recruitment was examined in mouse ileum after external gamma-irradiation (50 cGy) or internal beta-irradiation (0.148 MBq/g of [3H]thymidine), using the per cent-labelled-mitoses method and by analysing the distribution of mitotic cells in the crypts. In the presumptive stem cell zone at the lower cell positions of the crypt, the slowly cycling cells decreased their cell cycle 6 or 12 hours after a dose of 50 cGy. In the higher cell positions, a slight shortening of the cell cycle was also observed. After administration of a high dose of [3H]thymidine, dormant (G0) cells also entered the cell cycle in the lower cell positions. The results suggest that stem cells in the crypt may react to irradiation in two ways: first, by shortening the cell cycle in cycling cells; secondly, by an entry into the cell cycle by other dormant cells. There was destruction of some cycling stem cells before any recruitment. The data support the idea that the stem cell population in the crypt is heterogeneous.

The possibility of turnover of the epithelial duct cells was examined in the adult mouse pancreas by radioautography following continuous administration of 3H-thymidine for periods varying from 1 h to 60 days. One hour after an injection of 3H-thymidine, the label observed in small and large ducts was low but increased with the duration of the continuous infusion of 3H-thymidine and reached a level of about 67% cells labeled after 60 days. The rate of duct cell labeling was estimated from the regression line of the labeling index vs. time in four types of ducts classified according to their inner diameter and the presence of the adventitia and was given as 0.60% cells per day in small (adventitia-free) ducts (phi 4-12 micron), 0.89%, 1.02%, and 1.23% cells per day in large (adventitia-including) ducts (phi 15-29, 30-49, and 50-160 micron respectively). In contrast, the labeling index of aciner cells after a 60-day infusion indicated an addition of only 0.02-0.07% per day, and that of islet cells 0.14-0.22% per day. It is known that most parenchymal cells belong to either expanding or renewing cell populations. The acinar cells of the pancreas have been shown to constitute an expanding population, a conclusion confirmed by the low addition of cells observed in the present work. However, the relatively high rate of cell addition in the duct epithelia indicates that they may turn over in a period of 2.7 months in the case of large ducts and 5.6 months in the case of small ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

The acinar and islet cells of the adult mouse pancreas were examined by radioautography after continuous infusion of 3H-thymidine, for periods varying from 1 to 60 days, to determine whether they behaved like renewing or expanding cell populations. The labeling of both cell types increased with the duration of the continuous infusion and reached 2.22% and 12.0%, respectively, after 60 days. The rate of acinar and islet cell labeling was estimated from the regression line of the labeling index versus time and given as 0.039% and 0.20% cells per day, respectively. The rate of cell labeling was relatively low in these acinar and islet cells in comparison to the relatively high rate in duct cells. Occasionally, acinar cell labeling was not uniform, showing high labeling in the outer peripheral region of a lobe and at the periphery of the islets. Both acinar and islet cells increased in number in the adult, and at a rate indicating they are expanding cell populations. Their doubling times were estimated as 2,564 days (7.0 years) and 500 days (1.3 years), respectively. Duct epithelial cell populations were dividing at a rate indicating that they are renewing cell populations.