Deoxycholic Acid (DCA) has been linked to colorectal cancer (CRC) in humans and shown to increase tumor number in carcinogen exposed-rodents susceptible to developing CRC. However, the effect of DCA on a strain of mouse not sensitive to carcinogen exposure has been unstudied. 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% DCA. Mice placed on the DCA diet developed a significantly higher multiplicity of ACF compared to AOM-exposed mice fed a control diet. Interestingly, increased numbers of ACF were associated with the presence of nuclear β-catenin. In an effort to better understand the promotional role of DCA, the cryptal origins of DCA-exposed ACF were examined. Three ACF were serial-sectioned at 1 μm, followed by three-dimensional reconstruction. Under light microscopy, dysplastic cells protruding from the side of a normal-appearing crypt were observed in all ACF examined, in accordance with the budding model. This cryptal region was also found to harbor cells that stained positive for nuclear β-catenin. It is concluded that DCA promotes dysplasia in a resistant strain, potentially through nuclear β-catenin accumulation, and that the dysplasia originates from the middle of the crypt.
