• Circadian rhythms in the incidence of apoptotic cells and number of clonogenic cells in intestinal crypts after radiation using normal and reversed light conditions.

      Ijiri, K; Potten, Christopher S; Zoological Institute, Faculty of Science, University of Tokyo, Japan. (1988-05)
      Variations in the number of radiation-induced morphologically dead or dying cells (apoptotic cells) in the crypts in the small intestine of the mouse have been studied throughout a 24-h period under a normal light regimen (light on, 07.00-19.00 h; light off, 19.00-07.00 h). A clear circadian rhythm was displayed in the apoptotic incidence 3 or 6 h after irradiation for each gamma-ray dose studied (range 0.14-9.0 Gy). The most prominent circadian rhythm was obtained after 0.5 Gy. The peak time of day for inducing apoptosis was 06.00-09.00 h, and the trough occurred at 18.00-21.00 h. Some mice were also transferred to a room with the light cycle reversed, and were irradiated on different days after the transfer. The apoptosis induced by 0.5 Gy or 9.0 Gy, or the number of surviving crypts (microcolonies) after 11.0 Gy or 13.0 Gy was examined. The transition point for reversal (i.e. the switch time from the normal-light pattern to the reversed-light pattern) of the circadian rhythm in apoptosis (after 0.5 Gy) occurred 7 days after the transfer and the rhythm was reversed by 14 days. The rhythm for crypt survival (i.e. for clonogenic cell radiosensitivity) was disturbed on 1 day and the transition point for reversal occurred 3 days after the transfer. The rhythm became reversed by 7 days. These observations are discussed in relation to the identity of clonogenic cells, (functional) stem cells, proliferating transit cells and the cells sensitive to small doses of radiation (i.e. hypersensitive cells) in the crypt.
    • Radiation-hypersensitive cells in small intestinal crypts; their relationships to clonogenic cells.

      Ijiri, K; Potten, Christopher S; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Withington, Manchester, M20 9BX, UK. (1986)
    • The re-establishment of hypersensitive cells in the crypts of irradiated mouse intestine.

      Ijiri, K; Potten, Christopher S; Zoological Institute, Faculty of Science, University of Tokyo, Hongo, Tokyo 113, Japan (1984-11)
      Within 3-6 h of small doses of radiation (gamma-rays) the number of dead cells (apoptotic cells) in the crypts of the small intestine reaches peak values. These return to normal levels only after times later than 1 day. After higher doses elevated levels of cell death persist for longer times. The dead cells first occur most frequently at the lower positions of the crypt (median value for the distribution of apoptotic fragments is about cell position 6). At later times more dead cells are observed at higher positions. Two doses of radiation separated by various time intervals have been used to investigate when after irradiation the cell population susceptible to acute cell death is re-established. Dead cells were scored 3 or 6 h after the second dose. The yield of dead cells after two doses represents the sum of the dead cells produced by, and persisting from, the first dose and new apoptotic cells induced by the second dose. Since the temporal and dose-dependence aspects of the dead-cell yield after the first dose alone is known, the additional dead cells attributable to the second dose alone can be determined by subtraction. Within 1-2 days of small doses (0.5 Gy) the sensitive cells, recognized histologically as apoptotic cells, are re-established at the base of the crypt (around cell position 6). After higher doses (9.0 Gy) they are not re-established until about the fourth day after irradiation. Even in the enlarged regenerating crypts the sensitive cells are found at the same position at the crypt base. It has been estimated that the crypt contains five or six cells that are susceptible to low doses (0.5 Gy) (hypersensitive cells) and up to a total of only seven or eight susceptible cells that can be induced by any dose to enter the sequence of changes implicit in apoptosis. Between 4 and 10 days after an initial irradiation of 9.0 Gy the total number of susceptible cells increased from seven to eight to about 10 to 13 per crypt.
    • The recruitability and cell-cycle state of intestinal stem cells.

      Potten, Christopher S; Chadwick, Caroline A; Ijiri, K; Tsubouchi, S; Hanson, W R; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom (1984-03)
      Evidence is presented which suggests that the crypts of the small intestine contain at least two discrete but interdependent classes of stem cells, some with discrete cell kinetic properties and some with discrete radiation responses or radiosensitivities. Very low doses of X rays or gamma rays, or neutrons, kill a few cells in the stem cell regions of the crypt in a sensitive dose-dependent manner. Similar doses generate several different cell kinetic responses within either the clonogenic fraction or the cells at the stem cell position within the crypt. The cell kinetic responses range from apparent recruitment of G0 clonogenic cells into cycle, to a marked shortening of the average cell cycle of the cells at the stem cell position. It is suggested that the cell kinetic changes may be the consequence of the cell destruction.