The Circadian Rhythm for the Number and Sensitivity of Radiation-induced Apoptosis in the Crypts of Mouse Small Intestine

Summary

Apoptosis is a mode of cell death involving nuclear pycnosis, cytoplasmic condensation and karyorrhexis. Changes in the number of apoptotic cells at various times (3–12 h) after a single dose of either 0·5 or 9·0 Gy given at 09.00, 21.00 or 03.00 h were studied in histological sections of small intestinal crypts of mice. The incidences of apoptosis were examined 3 or 6 h after irradiation at different times of day with different doses of γ-rays ranging from 0·15 to 9·0 Gy. Survival curves were constructed from the dose–incidence curves for apoptosis, using the number of apoptotic cells after high doses (N_M) as the maximum cell population size. The mean lethal doses (D₀) for the dose range 0–0·5 Gy were calculated for each time of day. A circadian rhythm in both D₀ and N_M values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. A possible explanation based on the cell-cycle states of the target cell population for apoptosis (presumably functional stem cells) was drawn. Most of the target cells were assumed to be in an extended G₁ phase. Around 21.00 h a transition from G₁ to S phase takes place in some of these cells (approximately seven or eight cells per whole crypt). The S phase then lasts till around 06.00 h. They may be at G₂ and M around 06.00–09.00 h, and then they re-enter G₁. The circadian rhythm for the number and sensitivity of the cells susceptible to apoptosis obtained in the present report agrees well with this pattern of cell-cycle phases of target cells.