Effect of a Lithogenic Diet on Cell Proliferation in the Murine Gallbladder Epithelium

Abstract

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 < 0.01) and mitotic (p < 0.01) indices were observed from the 2nd day and the total DNA content of the gallbladder was increased (p < 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 < 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.

DNA synthesis, cell proliferation index in normal and abnormal gallbladder epithelium

“…It was proposed but not proved that increased bile secretion was involved but this dilatation remains unexplained. Also in the latter study there was no correlation between the degree of distension of the gallbladder and the proliferative parameters (Putz and Willems, 1981a).…”

Characterization of glycoproteins in the epithelial cells of human and other mammalian gallbladder: A review

“…Moreover, the enhancement of mucus secretion and an increase in mitosis before the formation of any precipitate have been described (Freston et al, 1969;Lee and Scott, 1982;Lee et al, 1981b;Pemsingh et al, 1987b;Putz and Willems, 1981;Scott, 1976). By using 3 H-glucosamine, Malet et al (1989) demonstrated that, in animals fed with a cholesterol-rich diet, mucin production increases twofold and sevenfold after 1 and 3 weeks, respectively.…”

Isolation, Culture, and Transplantation of Intrahepatic Biliary Epithelial Cells and Oval Cells

“…DNA synthesis and mitotic growth were further shown to be stimulated in vivo in the epithelial cells of murine gallbladder mucosa during feeding of a cholester ol-cholic acid lithogenic diet [119] and after chronic administration of cholecystokinin-octapeptide (CCK) or caerulein, a CCK analogue [120]. Chronic administra tion of 1.0% lithocholic acid in a low-protein diet to rats produced an intrahepatic biliary hyperplasia and peri cholangitis in vivo [121], but lithocholic acid was found to be toxic to primary cultures of normal rat intrahepatic bile ducts when added at concentrations above 0.5 mM and without effect below these concentrations [99].…”