Effect of a lithogenic diet on cell proliferation in the murine gallbladder epithelium

A cholesterol-cholic acid lithogenic diet was administered to mice for periods from 2 days to 12 weeks. Intraperitoneal injections of tritiated thymidine and autoradiographs were used for the estimation of the proliferative parameters in the gallbladder epithelium. The total DNA content of the gallbladder was determined. Significantly higher labeling (p less than 0.01) and mitotic (p less than 0.01) indices were observed from the 2nd day and the total DNA content of the gallbladder was increased (p less than 0.01) from the 2nd week of the diet. Increased proliferative activity was followed by hyperplasia of the gallbladder epithelium. A significant dilatation of the gallbladders was also noted from the 2nd day of the diet (p less than 0.01). Gallstones appeared after at least 4 weeks. Our results indicate that gallstone formation is preceded by a higher proliferative activity in the gallbladder mucosa. Distension of the gallbladder could be one of the factors explaining this phenomenon in mice, but the influence of intraluminal modifications in the bile salt composition cannot be excluded.