FIG. 9.
Radiation-induced injury of the ileum 1, 3, and 5 days after TBI of mice. C57BL/6NTac adult female mice were irradiated to the LD50/30 dose of 9.25 Gy TBI, and 12 h before sacrifice lavaged with 200 nm fluorescent beads (green). All procedures were preapproved and performed according to the protocols established by the Institutional Animal Care and Use Committee of the University of Pittsburgh. Samples were fixed, sectioned, and stained to show cellular apoptosis. (A), (D), and (G) are low power large area montages of entire bowel sections; (B), (E), and (H) are the inset panels from (A), (D), and (G); (C), (F), and (I) are the insets from (B), (E), and (H). In control animals (not shown), apoptosis is very rare and limited to epithelia in the villus apex. As can be seen from these image sequences, there is a clear and quantitative increase in the number of apoptotic cells (red) with time after irradiation. In addition, there is a coincident and concomitant increase in the number of particles escaping the luminal space into the adventitia and beyond. In (A) (1 day after irradiation), it can be seen that apoptosis is rare, limited to the epithelium (B) and primarily to the apex of the villus (C). Green particles do not escape the lumen of the ileum. In (D) (3 days after irradiation), it can be seen that although there is some increase in apical apoptosis, it is now continuous throughout the length of the villus, and also present within the cells of the serosa and adventitia (E). Further, as there is some collapse of villi, there is escape of beads from the lumen into the serosa (F). In (G) (5 days after irradiation), apoptosis is ubiquitous and villi structure is largely lost. Further, there is extensive penetration of beads into the serosa and adventitia as the ileum wall is compromised. All vertical columns are at the same magnification and defined in panels (A–C). TBI, total body irradiation. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars