title: Risk factors for colorectal cancer in man induce aberrant crypt foci in rats: Preliminary findings.
abstract: Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer, but the mechanisms responsible for these associations are not known. An animal model could facilitate such an understanding. Both genotoxic and nongenotoxic carcinogens induce aberrant crypt foci (ACF) in the colons of F344 rats. F344 rats were provided with diets that contained putative risk factors for CRC: low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure or a control diet for 14 wk. The rats were then assessed with biochemical measures and by topological examination for evidence of colon abnormalities. Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and ACF were increased from 0.7 to 13.6 lesions/colon (both P < 0.001). Rats exposed to the multiple environmental conditions associated with colon cancer, developed ACF similar to the heterogeneous or ill-defined ACF in the human colon. Heterogeneous ACF are the most frequently seen in humans and are also seen in rats shortly after exposure to the non-genotoxic colon carcinogen, dextransulfate sodium. The rodent model could be used to assess the pathways from diet and environment to colon cancer and to provide guidance for clinical studies.
authors.affiliation: a Faculty of Medicine, University of Toronto , Toronto , Canada.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: b Department of Nutritional Sciences , Faculty of Medicine, University of Toronto , Toronto , Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Fard
authors.affiliation: b Department of Nutritional Sciences , Faculty of Medicine, University of Toronto , Toronto , Canada.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Furrer
authors.affiliation: b Department of Nutritional Sciences , Faculty of Medicine, University of Toronto , Toronto , Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Archer
authors.affiliation: b Department of Nutritional Sciences , Faculty of Medicine, University of Toronto , Toronto , Canada.
authors.forename: W Robert
authors.initials: WR
authors.lastname: Bruce
authors.affiliation: c Department of Pharmaceutical Science , Faculty of Pharmacy, University of Toronto , Toronto , Canada.
authors.forename: HoYin
authors.initials: H
authors.lastname: Lip
authors.affiliation: c Department of Pharmaceutical Science , Faculty of Pharmacy, University of Toronto , Toronto , Canada.
authors.forename: Rhea
authors.initials: R
authors.lastname: Mehta
authors.affiliation: c Department of Pharmaceutical Science , Faculty of Pharmacy, University of Toronto , Toronto , Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Brien
authors.affiliation: d Department of Physiology , Faculty of Medicine, University of Toronto , Toronto , Canada.
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
authors.affiliation: e Centre for Bone and Muscle Health, Brock University , St. Catharines , Canada.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Ward
authors.affiliation: f NEUROFARBA Department , Section of Pharmacology and Toxicology, University of Florence , Florence , Italy.
authors.forename: A Pietro
authors.initials: AP
authors.lastname: Femia
authors.affiliation: f NEUROFARBA Department , Section of Pharmacology and Toxicology, University of Florence , Florence , Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Caderni
authors.affiliation: g Department of Pathology , Humber River Hospital , Toronto , Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Medline
authors.affiliation: h Division of Comparative Medicine and Department of Physiology, Faculty of Medicine, University of Toronto , Toronto , Canada.
authors.forename: Kate
authors.initials: K
authors.lastname: Banks
mesh_terms: D058739:Aberrant Crypt Foci / Q000209:etiology*; D000818:Animals; D002118:Calcium / Q000097:blood; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors
chemical_list: D002118:Calcium