Colonic mucus: secretion and turnover in relation to dietary fibre intake.

The colon is subjected to a myriad of potentially damaging agents that may reside within the lumen for 1-2 d. Its first line of defence against these agents is the protective mucus bilayer that lines the entire colonic mucosa. This bilayer acts as a physical barrier to mucosal aggressors and also reduces shear stress to the mucosa. These actions are dependent on the unstimulated ('resting') colonic mucus thickness, and also on the rate that this layer can be replenished. The colonic mucus layer is altered in a number of colonic diseases that have been linked to a deficiency of fibre in the diet. The action of fibre intake on colonic mucus thickness and secretion is unknown. Using an in vivo rat model it has been demonstrated that: (1). fibre deficiency leads to a decreased protective potential of the mucus layer (e.g. the mean resting mucus thickness of the fibre-deficient group (429 microm) was significantly lower than its respective control (579 microm; P< 0-001), as was its total mucus secretion over 6 h (270 microm v. 541 microm; P<0-01); (2). specific fibre types in the diet alter the secretion dynamics of colonic mucus (e.g. a cellulose-based diet reduces total mucus secretion over 6 h compared with its control (175 microm v. 463 microm). Analysis of the diets suggested a necessity for both soluble and insoluble fibre types in the diet to increase mucosal protection.

Abnormalities of the cadherin-catenin complex in chemically-induced colo-rectal carcinogenesis.

Beta-Catenin is a multifunctional protein originally identified as a component of the cadherin cell-cell adhesion complex. It also binds the adenomatous polyposis coli (APC) tumour suppressor which controls beta-catenin cellular levels through its degradation. (beta-Catenin and/or APC mutations result in increased cytoplasmic Beta-catenin and nuclear translocation. The aim of the present study was to examine the expression and cellular localisation of alpha and beta-catenin, p120 and E-cadherin in a chemically-induced mouse model of colo-rectal cancer using 1,2-dimethylhydrazine (DMH). Female Balb/C mice were injected subcutaneously with a solution providing 25 mg DMH base/kg body weight for 17 weeks. Animals were killed and tumours identified in the intestine with a dissecting microscope. Formalin-fixed paraffin-embedded sections of normal and dysplastic colonic mucosa were stained by an indirect avidin-biotin immunohistochemical technique using mouse monoclonal antibodies, and membranous, cytoplasmic and nuclear cellular localisation was assessed by light microscopy. Staining distribution scored as follows: 3, > 90 % positive epithelial cells; 2, >50 % positive epithelial cells; 1, <50 % positive epithelial cells. Non-dysplastic colonic epithelial cells revealed beta-catenin expression at the membrane (33/41 scored 3),areas of cytoplasmic expression (24/41 scored 1) and no nuclear staining. Dysplastic colonic epithelium revealed increased membranous and cytoplasmic, beta-catenin immunoreactivity (39/41 and 38/41 both scored 3) with focal nuclear staining (14/41). Expression patterns for ac-catenin, p120, and E-cadherin were similar to beta-catenin with increased membranous and cytoplasmic immunoreactivity in dysplastic mucosa, although no nuclear staining was observed. Increased cytoplasmic expression and nuclear localisation of beta-catenin are consistent with a possible mutation in its gene, and this finding was in keeping with the mutational analysis of exon 3 by single-strand conformational polymorphism. Increased immunoreactivity of the other catenins also suggests further disruption in catenin regulation. In summary, alterations in the beta-catenin expression and cellular localisation in the DMH-induced tumours are similar to those seen inhuman sporadic colorectal tumours. The DMH is therefore a useful model for studying the abnormalities of the E-cadherin-catenin pathway in colorectal carcinogenesis.