The effect of local hyperthermia on nonproliferative, compared with proliferative, epithelial cells of the mouse intestinal mucosa.

The effects of local hyperthermia on different components of mouse intestinal mucosa were investigated. The intestine was heated by immersion in Krebs-Ringer solution at various times after intraperitoneal injection of [3H]thymidine, and thermal injury was assessed by measuring loss of label. The interval between labeling and heating was either 14 hr, when the majority of labeled epithelial cells were still in the crypts, or 65-72 hr, when the majority of the label had moved onto the villi. Heating at 42 degrees C for up to 1 hr had no observable effect. When intestine was heated at 43 degrees C 14 hr after labeling, the characteristics of the loss of label were very similar to loss of crypts with regard to both the fraction lost and the time over which the response occurred. The threshold heating time to cause an effect was between 20 and 30 min and the response was complete by 6 hr after treatment. If, however, intestine was heated at 43 degrees C either 65 or 72 hr after injection of [3H]thymidine, the threshold heating time required to cause an effect was reduced to between 10 and 20 min and loss of label was not necessarily accompanied by crypt loss. For example, 40% of radioactivity could be lost from the villi without any corresponding loss of crypts. Both the labeling experiments and histological examination indicated that the nonproliferative cells of the intestinal mucosa that line the lumen are more susceptible to thermal injury than the crypt cells. Thus, although crypt loss may remain a useful endpoint in the assessment of thermal damage, the data would underestimate early mucosal injury and the impairment of functional integrity of small intestine.