title: Resistant carbohydrates stimulate cell proliferation and crypt fission in wild-type mice and in the Apc(Min/+) mouse model of intestinal cancer, association with enhanced polyp development.
abstract: Fermentation of carbohydrates in the colon can stimulate cell proliferation and could thus be a cancer risk. The effects of resistant carbohydrates, i.e. those not digested and absorbed in the small intestine, on cell proliferation, crypt fission and polyp development were investigated in wild-type and adenomatous polyposis coli multiple intestinal neoplasia (Apc(Min/+)) mice. Fifteen 4-week-old female wild-type and fifteen Apc(Min/+) mice were used for each group and fed a chow diet, a semi-synthetic diet or the semi-synthetic supplemented with wheat bran or an apple pomace preparation, both high in resistant carbohydrates, for 8 weeks. Tissue from all mice was used to measure cell proliferation and crypt fission and tissue from the Apc(Min/+) mice was scored for polyp number and tumour burden. There were slight reductions in intestinal mass in the mice fed the semi-synthetic diets and this was increased by the inclusion of resistant carbohydrates. The Apc(Min/+) mice had elevated cell proliferation and crypt fission in the distal small intestine and colon and these were increased by the resistant carbohydrates. Bran or apple pomace significantly increased polyp number in the proximal third of the small intestine. Apple pulp more than doubled polyp number throughout the small bowel (99.2 (SEM 11.1) v. 40.0 (SEM 8.2), P<0.004). Bran and apple pomace increased polyp diameter and hence burden in the colon by 243 and 150 %, respectively (P<0.05). In conclusion, both types of resistant carbohydrates increased polyp number and tumour burden and this was associated with elevated epithelial cell proliferation and crypt fission.
authors.affiliation: Histopathology Unit, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A3PX, UK.
authors.forename: Nikki
authors.initials: N
authors.lastname: Mandir
authors.forename: Hans
authors.initials: H
authors.lastname: Englyst
authors.forename: Robert A
authors.initials: RA
authors.lastname: Goodlad
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000473:pathology*; D000818:Animals; D049109:Cell Proliferation; D003106:Colon; D004043:Dietary Fiber / Q000008:administration & dosage*; D005260:Female; D005285:Fermentation; D017491:Genes, APC; D007413:Intestinal Mucosa / Q000473:pathology*; D007417:Intestinal Polyps / Q000473:pathology*; D007421:Intestine, Small; D027845:Malus; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009929:Organ Size; D013154:Spleen / Q000473:pathology