Radiation-induced crypt intestinal epithelial cell apoptosis in vivo involves both caspase-3-dependent and -independent pathways.

Caspases play a major role in virtually all forms of apoptosis. Radiation is well known to induce apoptosis of crypt intestinal epithelial cells (IEC). Here, we examined the role of caspase-3 in radiation-induced IEC apoptosis. We demonstrate that while caspase-3 is present in IEC and activated upon irradiation, IEC in caspase-3-deficient mice partially underwent radiation-induced apoptosis. Typical morphological changes of IEC undergoing radiation-induced apoptosis (ie, blebbing, shrinkage, and nuclear condensation) can occur independently of caspase-3; however DNA fragmentation, as analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, is mostly, but not entirely, caspase-3-dependent. Overall, these results demonstrate that radiation-induced crypt IEC apoptosis has both caspase-3-independent and -dependent components.