The Doubling Time of Regenerating Clonogenic Cells in the Crypts of the Irradiated Mouse Small Intestine

Abstract

The number of clonogenic cells per intestinal crypt has been estimated in control and gamma-irradiated mice, from the response to a single or two test doses. Control unirradiated mice contained 43 +/- 8 clonogenic cells per crypt, which was reduced to about 3 per crypt immediately after 8.0 Gy. After a mitotic delay which was approximately 18 h or 2.25 h/Gy the number of clonogenic cells per crypt increased exponentially with a doubling time of 21 +/- 4 h to reach the control values by about the 4th day postirradiation. The growth curve was related to the changes in total cellularity and the cell production rate per crypt. Since both of these rise during the period of clonogenic regrowth some clonogenic cells must be diverted into the dividing transit cell population, so that the cell cycle time will be shorter than the doubling time given above.

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

“…Such a dose reduces the number of clonogenic cells per crypt to between 1 and 3 (Potten and Hendry 1975, 1988 with the sterilization of very few crypts (Withers andElkind 1970, Potten andHendry 1985) . Thus, virtually all crypts pass through the process of clonogenic repopulation, with a possible overshoot in both clonogenic and non-clonogenic cell numbers during the time course of the present experiments .…”

“…The kinetics of the shrinkage in total crypt cellularity has been studied, together with the timing of compensatory increases in proliferation at each cell position within the crypt structure, and hence within the crypt cell hierarchy (Potten and Hendry 1983) . These changes can be compared with the known repopulation kinetics for the clonogenic cell compartment (Potten and Hendry 1975, Hendry, 1979, Potten et al . 1988) and the changes observed histologically in crypt size, particularly before the assessment of survival using the microcolony technique (Withers andElkind 1970, Potten andHendry 1985) .…”

The significance of spontaneous and induced apoptosis in the gastrointestinal tract of mice

“…1 [2,9]. The precise number of lineage ancestor cells (stem cells) remains unclear but is probably within the range of 4-16 for the small intestine and in the range 1-4 for the large bowel [8][9][10][11]. One of the unique features of this tissue is that the position of a cell in the hierarchy can be related to its topographical position within the crypt in the manner that is illustrated in Fig.…”

Protective Effect of an Extract of Emblica officinalis Against Radiation-Induced Damage in Mice

“…35 These findings are comparable to those of Quastler, 36,37 Devik, 38 and Singh, 39 who observed that after irradiation a considerable fraction of the cells die during the initial mitotic depression without undergoing cell division. Potten et al 40 explained the reduction in crypt cellularity on the basis that migration of cells from the crypt to the villus continues over the first 24 hours post-irradiation in spite of the fact that cell division is inhibited or severely reduced. Similarly, Nandchahal 41 exposed mice to 3 different doses (4.5, 9.0, and 12 Gy) of whole-body γ radiation and found that total populations of crypt cells was significantly decreased on day 1.…”