deoxycholic-acid and Gallbladder-Neoplasms

Topics: Adenosine; Animals; Cell Line, Tumor; Cell Proliferation; Deoxycholic Acid; Disease Progression; Gallbladder Neoplasms; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Male; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; RNA Interference; Xenograft Model Antitumor Assays

The role of biliary deoxycholate as an endogenous carcinogen and the possible association between cholelithiasis and the subsequent development of carcinoma of the gall bladder is unclear. This paper describes biliary bile acid analysis performed on three groups of patients, 10 with cholelithiasis, 10 with carcinoma of the gall bladder and 10 control patients. This is the first report of bile acid changes in carcinoma of the gall bladder. In these 30 patients the total bile acids concentration was highly variable (11.44-53.68 mg/ml). The mean ratio of primary to secondary bile acids was 3.5:1. This ratio was, however, significantly higher in cholelithiasis than in the control group (5.34:1; P < 0.001); patients with carcinoma of the gall bladder had significantly higher secondary bile acids (1:1; P < 0.001). This is due to a marked increase in the secondary bile acids and indicates that raised biliary deoxycholate concentrations are present in patients with carcinoma of the gall bladder and therefore may well be a factor in carcinogenesis.

Topics: Bile Acids and Salts; Carcinoma; Chenodeoxycholic Acid; Cholelithiasis; Cholic Acid; Cholic Acids; Deoxycholic Acid; Gallbladder Neoplasms; Humans; Lithocholic Acid

The effects of dietary administration of phenobarbital [(PB) CAS: 50-06-6] or the secondary bile acids, deoxycholic acid [(DCA) CAS: 83-44-3] and lithocholic acid [(LCA) CAS: 434-13-9], on tumorigenesis in the liver, gallbladder, and pancreas were investigated in male Syrian golden hamsters after carcinogenic initiation by N-nitrosobis(2-hydroxypropyl)amine [(BHP) CAS: 53609-64-6]. BHP [500 mg/kg (body wt)] was injected sc once weekly for 5 weeks. The animals were then maintained on a basal diet or a diet containing either 0.05% PB, 0.1% DCA, 0.5% DCA, or 0.5% LCA for 30 weeks. DCA enhanced the development of cholangiocarcinomas without influencing that of hepatocellular lesions. PB promoted the induction of hepatocellular carcinomas but not that of cholangiocarcinomas. LCA was without effect on the induction of either hepatocellular carcinomas or cholangiocarcinomas. DCA at a dose of 0.5% enhanced the induction of polyps in the gallbladder. Both DCA, at a dose of 0.1%, and LCA significantly enhanced the induction of pancreas carcinomas. PB had no effect on the induction of polyps in the gallbladder or of pancreas carcinomas. These data document that different tumors may be differentially promoted following initiation with a common carcinogen.

Topics: Adenoma, Bile Duct; Animals; Bile Acids and Salts; Cocarcinogenesis; Cricetinae; Deoxycholic Acid; Eating; Gallbladder Neoplasms; Lithocholic Acid; Liver Neoplasms, Experimental; Male; Mesocricetus; Nitrosamines; Organ Size; Pancreatic Neoplasms; Phenobarbital; Polyps