Radiation-induced mitotic delay: duration, dose and cell position dependence in the crypts of the small intestine in the mouse.
AffiliationPaterson Laboratories, Christie Hospital & Holt Radium Institute, Manchester, M20 9BX, U.K.
MetadataShow full item record
AbstractThe cells of the proliferative compartment in the crypt of the small intestine undergo a step by step differentiation and/or maturation from stem cells to the functional cells on the villi. The consequent hierarchical organization of the proliferative cell population can be related to the actual position of cells within the crypt. The stem cells are found near the bottom of the crypt with the more mature cells occurring at increasingly higher positions. The sensitivity of proliferative cells in the crypt of small intestine to radiation-induced mitotic delay was investigated at each position within the crypt. Using the stathmokinetic method (vincristine accumulation), the following were noted. The yield of mitotic figures 3 h immediately after irradiation showed a strong cell position dependence with the cells at the base of the crypt being most inhibited and those at the top of the proliferative compartment least affected. The mitotic yields were largely unaffected for the first 15 min suggesting that there is a transition point (Tp) for radiosensitivity which is located about 15 min before metaphase for all crypt cells. Cells located less than 15 min from metaphase are unaffected while those more than 15 min from metaphase are inhibited from further cell cycle progression. After this initial delay all proliferative cells were inhibited in their progression through G2 but some recovered more quickly than others. The ratio of the time of division delay (Td) in stem cells to that in cells at the top of the proliferative compartment was about 3:1. In absolute values Td after 1.0 Gy was about 1 h and 2.8 h, for cells at the top of the crypt and at the base, respectively. After 2.5 Gy the corresponding values were less than 3 h and between 5 and 6 h for the mid-crypt and crypt base respectively. There is thus a dependence on dose for the duration of the mitotic inhibition which for the cells at the top of the crypt is similar to the widely quoted average value 1 h per Gy, but the duration depends strongly on cell position. Thus not all proliferative cells respond in the same way. The duration is shorter the closer the proliferative cells are to their last cell division in the proliferative hierarchy in the crypt and longest for cells situated where the stem cells are to be expected.
CitationRadiation-induced mitotic delay: duration, dose and cell position dependence in the crypts of the small intestine in the mouse. 1986, 49 (5):809-19 Int J Radiat Biol Relat Stud Phys Chem Med
JournalInternational Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine
- The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine.
- Authors: Potten CS, Grant HK
- Issue date: 1998 Oct
- The effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine.
- Authors: Potten CS, O'Shea JA, Farrell CL, Rex K, Booth C
- Issue date: 2001 May
- The temporal and spatial changes in cell proliferation within the irradiated crypts of the murine small intestine.
- Authors: Potten CS, Owen G, Roberts SA
- Issue date: 1990 Jan
- Intestinal crypt proliferation. II. Computer modelling of mitotic index data provides further evidence for lateral and vertical cell migration in the absence of mitotic activity.
- Authors: Loeffler M, Potten CS, Paulus U, Glatzer J, Chwalinski S
- Issue date: 1988 Jul
- The effect of proliferative status and clonogen content on the response of mouse jejunal crypts to split-dose irradiation.
- Authors: Thames HD, Ruifrok AC, Mason KA
- Issue date: 1997 Feb