Intestinal proliferation after multiple fractions of gamma irradiation

The histologic appearance of intestinal mucosa in BALB/c⁺ mice was studied after fractionated irradiation. Daily doses of 200 and 350 rad were given to the abdomen to investigate recovery mechanisms. After 200 rad/day (1000 rad/week), the average number of nuclei per tangential section of crypts increased in two steps and reached 117, 112, 151, 140, and 145% of the control value after 2, 3, 4, 5 and 6 weeks. The average numbers of mitoses and of [³H]thymidine-labeled nuclei per crypt also increased to 155, 155, 160, 207, and 221% and 190, 140, 131, 192, and 230% of the controls, respectively. These data suggest an increase in the stem cell compartment, which is estimated at 1.4 times its normal value after 4 to 6 weeks. The length of the mitotic cycle Tc was measured using the usual [³H]thymidine labeling technique after 5000 rad/5 weeks, given in daily fractions of 200 rad. Tc was reduced from 14 to 9 hr, this reduction mainly concerning the G₁ phase (from 5 to 1 hr) and to a smaller extent the S phase (from 7 to 6 hr). Intestinal mucosa tends to compensate for cell destruction by two mechanisms: a reduction in the duration of the mitotic cycle and an increase in the size of the stem cell compartment. At 200 rad/day, an important compensation is achieved and the animals are able to tolerate the irradiation for about 6 weeks. At 350 rad/day, however, increased cell production can no longer compensate for cell destruction and the animals die after the third week.