3rd Annual BMRP Investigator Meeting - Abstract
Effects of Deoxycholic Acid and Ursodeoxycholic Acid on the Development of Carcinomas during Murine Chronic Ulcerative Colitis
Christoph Hanski1,a, Christoph Loddenkemper2 and Martin Zeitz1
1Medizinische Klinik I and 2Institut für Pathologie, Charité Universitatsmedizin Berlin, Campus Benjamin Franklin (Berlin, Germany)
Background: Recent retrospective studies on patients with primary sclerosing cholangitis (PSC) associated with ulcerative colitis indicates that the standard treatment of PSC with ursodeoxycholic acid (UDCA) contributes to the decrease of the risk of developing colon carcinoma. The anticarcinogenic mechanism of UDCA action is not known; the suppression of inflammation as well as effect on proliferative and apoptotic pathways is discussed.
Aim: To establish a murine model in which colitis-related colon carcinogenesis is suppressed by UDCA treatment.
Methods: Three groups of mice (25 each) were fed with a diet containing 90 mg/kg iron and given water with 0.1% dextran sulfate (for seven days) or without additives (for ten days). One group was fed with 0.4% cholic acid (CA) and another with 0.4% UDCA in the diet. Tumor development was followed endoscopically. The feces were collected, total bile acids extracted and the concentration of CA, DCA and UDCA in fecal water determined by HPLC and MS. After 16 cycles, the mice were killed and the colons histologically investigated.
Results: 96% of the control group, 60% of the CA group and 80% of the UDCA group survived the treatment. Tumors were visible by endoscopy already after ten cycles; their nature (hyperplasia, adenoma, carcinoma) could be identified by histology. The frequency and multiplicity of the tumors in each group will be compared with the grade of inflammation and with the concentration of the bile acids in the fecal water. This model may allow investigation of the anticarcinogenic mechanism of UDCA during colitis-related colon carcinogenesis.
aPrincipal Investigator