deoxycholic-acid and Hyperplasia

Topics: Body Contouring; Deoxycholic Acid; Female; Humans; Hyperplasia; Middle Aged; Subcutaneous Fat, Abdominal

Topics: Adiposity; Deoxycholic Acid; Humans; Hyperplasia; Injections; Obesity; Subcutaneous Fat

AKR/J mice are resistant to the tumorigenic properties of the colon carcinogen, azoxymethane (AOM). Following AOM exposure, limited numbers of preneoplastic lesions, referred to as aberrant crypt foci (ACF), are formed in the colon, and their progression to tumors rarely occurs. To determine whether genetic resistance can be overcome by exposure to a dietary tumor promoter, AOM-exposed AKR/J mice were fed a diet containing 0.25% deoxycholic acid (DCA). DCA exposure was begun 1 wk prior to or 1 wk after tumor initiation with AOM. Mice placed on the DCA diet prior to AOM treatment developed a significantly higher multiplicity of ACF compared to AOM-exposed mice fed a control diet (15.50 +/- 0.96 vs. 6.17 +/- 0.48, respectively; P < 0.05). When DCA exposure was begun after AOM treatment (post-initiation), ACF formation was further enhanced (34.00 +/- 1.22). Interestingly, increased numbers of ACF were associated with the presence of nuclear beta-catenin, assessed by immunohistochemistry. While approximately 33% of ACF from mice exposed to DCA prior to AOM treatment contained positive nuclear beta-catenin staining, approximately 77% of ACF from mice fed DCA after AOM were positive. Accumulation of nuclear beta-catenin was not associated with a loss of E-cadherin from the plasma membrane, although loss of APC staining was a consistent feature of most AOM-induced ACF, regardless of DCA exposure. These results demonstrate that exposure to DCA, an important digestive component, is sufficient to sensitize the resistant AKR/J colon to formation of high-grade dysplasia, and that nuclear translocation of beta-catenin may play an important role in this process.

Topics: Animals; Azoxymethane; beta Catenin; Cadherins; Carcinogens; Cell Nucleus; Colon; Colonic Neoplasms; Deoxycholic Acid; Detergents; Hyperplasia; Male; Mice; Mice, Inbred AKR; Precancerous Conditions; Protein Transport

The initiating potential of the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), was investigated using the development of preneoplastic lesions in the rat liver as a marker. In a short-term assay in which DCA and LCA were given in the diet for 3 weeks in conjunction with partial hepatectomy midway followed by the selection regimen, DCA dose-dependently induced gamma-glutamyltranspeptidase (gamma-GTP)-positive foci, but the results for LCA were less unequivocal and no dose-dependency was evident. In another experiment, I extended the period of observation and examined whether the gamma-GTP-positive foci thus induced by the secondary bile acids can develop into hepatic tumors after a latent period of 52 weeks with or without the administration of phenobarbital (PB), a promoter of experimental hepatocarcinogenesis. Whereas significantly high numbers of hyperplastic liver nodules developed in the DCA-treated rats irrespective of PB promotion, no such increase was evident in the LCA-treated rats. In contrast, both DCA and LCA treatments enhanced the development of glutathione S-transferase placental form (GST-P)-positive foci with or without subsequent PB promotion. The present data indicate that a short period of administration of DCA and LCA in the initiation stage in conjunction with partial hepatectomy results in enhanced development of preneoplastic liver lesions under selection pressure conditions with or without subsequent PB promotion. This suggests that these secondary bile acids possess possible initiating activity for rat hepatocarcinogenesis.

Topics: Animals; Carcinogens; Deoxycholic Acid; gamma-Glutamyltransferase; Hyperplasia; Lithocholic Acid; Liver; Liver Neoplasms; Male; Rats; Rats, Inbred F344

Severe epithelial hyperplasia was produced in a canine model by the perfusion of the main pancreatic duct with 15 mM of deoxycholate at rates as low as 1.5 ml/day in 6 to 14 days. At higher rates (5 ml/day) deoxycholate caused complete epithelial cell lysis in the duct closest to the tip of the cannula with hyperplastic changes downstream from this section. Perfusion with a buffer solution alone and cannulation alone produced none of these changes in similar duct segments. No hyperplasia was seen in the upstream cannula obstructed duct, even in the presence of severe atrophy. Long-term (81 days) perfusion with 3 mM of deoxycholate at 3 ml/day resulted in more severe hyperplasia that still appeared benign. When glycine-conjugated deoxycholate was perfused through the duct, hyperplasia but no cell lysis was seen. In vitro, deoxycholate caused epithelial cell lysis in pancreatic duct fragments at concentrations of 0.5 mM and above. The results of this study suggest that secondary bile salts or other similar surface-active cytotoxic agents present in the biliary tree or duodenum may play a more important role in the pathogenesis of pancreatic ductal epithelial hyperplasia associated with pancreatic cancer than ductal obstruction.

Topics: Animals; Bile Reflux; Deoxycholic Acid; Dogs; Epithelium; Hyperplasia; In Vitro Techniques; Pancreatic Ducts

The protein in microsomal membranes of hyperplastic nodules of livers from rats fed a diet containing 2-acetyl-aminofluorene referred to as the preneoplastic antigen has been purified to a nearly homogeneous state. A protein sharing identical immunodeterminants based on double agarose diffusion and immunoelectrophoresis has also been detected in deoxycholate-solubilized microsomes from normal liver, but it cannot be detected by gel immunodiffusion in the absence of detergent. There is approximately 4 times as much of this antigen in hyperplastic nodule microsomes as there is in normal microsomes as determined by electroimmunoassay. The antigen from nodules is not more than one-half the molecular weight of the antigen derived from normal microsomes in 0.2% deoxycholate. These findings are consistent with the hypothesis that an altered state of membranes exists in hyperplastic nodule endoplasmic reticulum, resulting in increased amounts of immunoreactive preneoplastic antigen. The nodule protein has a decreased association with its membrane matrix.

Topics: 2-Acetylaminofluorene; Animals; Antigens, Neoplasm; Deoxycholic Acid; Hyperplasia; Immunosorbent Techniques; Liver Neoplasms; Male; Microsomes, Liver; Neoplasms, Experimental; Precancerous Conditions; Rats

Total and free ribosomes were isolated from postnuclear supernatants of trypsinized normal and 3-methylcholanthrene-treated epidermis from female CD-1 mice. Membrane-bound ribosomes were determined as the calculated difference between total and free ribosomes. The value for total ribosomes from normal epidermis in the resting phase of the hair growth cycle was 0.32 mg. of ribosomal RNA per gm. of epidermis, or 0.07 mg. of ribosomal RNA per mg. of homogenate DNA. About 96 per cent of the ribosomes were free and 4 per cent were membrane-bound. Five days after a single application of 2 mu moles of 3-methylcholanthrene to the dorsal skin in the resting phase of the hair growth cycle, there was epidermal hyperplasia and cellular hypertrophy. Total ribosomes increased 2- to 3-fold, to 0.80 mg. of ribosomal RNA per gm. of epidermis, or 0.21 mg. of ribosomal RNA per mg. of homogenate DNA. This increase was further characterized as proportionate increases of both free and membrane-bound ribosomes.

Topics: Animals; Biopsy; Buffers; Cell Membrane; Deoxycholic Acid; DNA; Female; Hair; Hyperplasia; Hypertrophy; Liver; Methylcholanthrene; Mice; Polyethylene Glycols; Potassium Chloride; Ribosomes; RNA, Ribosomal; Skin; Subcellular Fractions; Trypsin