Abstract
The health risks incurred when children are exposed to radiation is a problem receiving increased attention. To understand how radiation affects the developing intestine, we examined the intestine of X-irradiated C57BL/6J mice, including neonates, infants, and adults. Intestinal development progressed in three stages: crypt neogenesis pre- and immediately postpartum, crypt fission/branching during infancy, and crypt-villus architectural maturation after weaning. Irradiated adult small intestinal crypts displayed two separate apoptotic waves (as defined by the presence of caspase-3)—the first wave peaked at 3 hr and was followed by a broad wave with a peak persisting from 24 to 48 hr. During the first wave, p53 was expressed, whereas it was not during the second wave. For infant small intestine, the intensity of the first wave was approximately half that of the adult wave, and for the colon the intensity was smaller yet. The second wave was also diminished in infant crypts. In neonates, apoptosis was delayed, peaking at 6 hr for small intestinal crypts and at 24 hr for colonic crypts—apoptotic crypts were absent at 3 hr. Apoptosis of the cells of adult small intestinal crypts was greatest at position 4 but occurred uniformly in infant crypts. Colonic cells at positions 1 and 2 were the most susceptible to radiation, regardless of age. Although no apoptosis occurred at 3 hr post-irradiation in neonates, p53 was induced in small intestinal inter-villi clefts and in colonic crypts. This finding suggests that p53 expression and apoptosis are unrelated during development of the neonatal intestine. Conversely, p21WAF-1/CIP1 expression was greater in neonatal crypt cells than in those of adults, suggesting efficient cell cycle arrest in neonates. Apparently, the developing intestine exhibits unique apoptotic responses to irradiation that are distinct from those of the adult intestine.
