Figure 3.

Inhibition of proliferation by treatment with Ara-C. A) Experimental strategy for monitoring migration of IdU-labeled cells on the villi and cell proliferation within the crypts after Ara-C administration. B) Images of labeled ileum sections at several sampling times illustrating that at the time of Ara-C administration, the IdU-labeled cells had already reached the villi, BrdU uptake was not detected, and mitosis was reduced during the first 10 h after Ara-C administration but recovers at later times. C) Number of mitotic events detected by pH3 staining after Ara-C injection. D) The proportion of crypt cells incorporating BrdU 18 h after Ara-C injection (continuous line) was similar to that observed in nontreated animals (dashed line). E–H) Fit of the 2-compartment model (lines) to observed numbers of labeled cells (circles) in the crypt and villus of mice treated with Ara-C. Proliferation within the crypt and cell transfer to the villus were blocked during the first 10 h after Ara-C administration in duodenum (E) and ileum (F) and resumed in both tissues at later time points (G, H, respectively). I) Comparison of net cell production rates in the crypts of control and Ara-C-treated mice. Asterisks: statistically significant differences. Statistical inference methods and results are in Materials and Methods and Supplemental Fig. 3.