The electrical and sodium transport characteristics of sutured premalignant mouse colon

Abstract

Depolarization of the plasma membrane and increased sodium influx have both been suggested as mitogenic signals. Following bowel resection the intestinal suture line has been reported a fertile site for tumor recurrence. Whether alterations in cell surface signaling occur at suture lines has not been previously examined. Therefore in this series of experiments we have examined the electrical changes and sodium transport occurring at a suture line in an animal model of large bowel cancer. Forty-eight female CF 1 mice underwent colotomies with repair utilizing silk or chromic sutures. Twenty-four mice underwent sham operations to serve as controls. The mice were injected subcutaneously with the carcinogen DMH (1,2-dimethylhydrazine) 20 mg/kg or an identical volume of 0.9% saline for 6 weeks and were sacrificed 1 week after the last injection. The sites of the sutured colotomies or a piece of distal colon from the sham-operated mice were mounted in a modified Ussing chamber and the electrical properties and unidirectional sodium fluxes were measured. The potential difference (pd) across the distal colon was not significantly different in any suture group compared to that in sham-operated controls when treated with saline (pd sham, −2.3 ± 0.2 mV (mean ± SEM); silk, −1.7 ± 0.3 mV, chromic, −1.9 ± 0.3 mV, P > 0.05, unpaired Student t test). The potential difference was significantly lowered in both suture groups compared to sham operated animals after treatment with DMH (pd sham, −2.6 ± 0.3 mV; silk, −1.5 ± 0.2 mV, P < 0.05; chromic, −1.6 ± 0.4 mV, P < 0.05). Although the pd in sham-operated controls and sham-operated DMH animals were lower than previously reported, this experiment demonstrated that depolarization occurred across the colon adjacent to an intestinal suture line after treatment with DMH. The lower pd in both sham groups may be due to stress, particularly in the sham-operated DMH group where unidirectional fluxes demonstrated a fourfold increase in net sodium absorption when compared to controls. Unidirectional fluxes of 22Na were significantly altered by DMH-treatment or the placement of bowel sutures. Epithelial depolarization and altered sodium transport have been observed at different stages during experimental carcinogenesis and following malignant transformation; therefore these effects on the electrophysiologic properties of large bowel mucosa induced by suture material may partly explain the mechanism of suture line recurrence.