Stimulation of thymidine incorporation in mouse liver and biliary tract epithelium by lithocholate and deoxycholate

Abstract

Lithocholate produces bile duct and ductular cell hyperplasia, and adenomatous hepatic nodules. The early effects of lithocholate and related bile salts on the liver and biliary tract were investigated by measuring tritiated thymidine (3HTdR) incorporation into DNA after single oral doses of bile salts. Lithocholate, in doses of 12.5 mg and above, enhanced incorporation of 3HTdR at 28 and 36 hr in gallbladder epithelium and at 36 hr in hepatocytes. Areas of hepatocellular necrosis, resembling the lesions of peliosis hepatis, occurred with 12.5- and 25-mg doses of lithocholate, but were not seen with deoxycholate, cholate, chenodeoxycholate, ursodeoxycholate, or hyodeoxycholate. Deoxycholate, and to a lesser extent cholate, also stimulated 3HTdR incorporation in both liver and gallbladder, but chenodeoxycholate did not. These studies suggest that certain bile acids rapidly exert major effects on cell kinetics in the liver and biliary tract, and that these effects depend on the structure of the bile acid molecule. Bile duct (organ) hyperplasia induced by lithocholate must depend on additional factors. The stimulation of proliferative activity by certain (particularly secondary) bile acids may have important consequences for tissues and organs exposed to the bile acid pool during its enterohepatic circulation and subsequent excretion via the colon.