The circadian rhythm for the number and sensitivity of radiation-induced apoptosis in the crypts of mouse small intestine

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 gamma-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 (NM) as the maximum cell population size. The mean lethal doses (Do) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both Do and NM 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.