title: Impact of dextran sulphate sodium-induced colitis on the intestinal transport of the colon carcinogen PhIP.
abstract: Colorectal cancer is one of the most frequent cancers in Western countries. Chronic intestinal diseases such as Crohn's disease and ulcerative colitis, in which the intestinal barrier is massively disturbed, significantly raise the risk of developing a colorectal tumour. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a genotoxic heterocyclic aromatic amine that is formed after strongly heating fish and meat. In this study, the hypothesis that PhIP uptake in the gut is increased during chronic colitis was tested. Chronic colitis was induced by oral administration of dextran sulphate sodium (DSS) to Fischer 344 rats. The transport of PhIP in eight different rat intestinal segments was examined in Ussing chambers. The tissues were incubated with 10 µM PhIP for 90 min, and the concentration of PhIP was determined in the mucosal and serosal compartments of the Ussing chambers as well as in the clamped tissues by LC-MS. Although chronic colitis was clearly induced in the rats, no differences in the intestinal transport of PhIP were observed between control and DSS-treated animals. The hypothesis that in the course of chronic colitis more PhIP is taken up by the intestinal epithelium, thereby increasing the risk of developing colorectal cancer, could not be confirmed in the present report.
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Nicken
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: von Keutz
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Willenberg
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany.
authors.forename: Annika I
authors.initials: AI
authors.lastname: Ostermann
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany.|Institute of Food Chemistry, University of Wuppertal, 42119, Wuppertal, Germany.
authors.forename: Nils Helge
authors.initials: NH
authors.lastname: Schebb
authors.affiliation: Department of Veterinary Pathology, Freie Universität Berlin, 14163, Berlin, Germany.
authors.forename: Samoa
authors.initials: S
authors.lastname: Giovannini
authors.affiliation: Department of Veterinary Pathology, Freie Universität Berlin, 14163, Berlin, Germany.
authors.forename: Olivia
authors.initials: O
authors.lastname: Kershaw
authors.affiliation: Department of Physiology, University of Veterinary Medicine Hannover, Foundation, 30173, Hannover, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Breves
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany. pablo.steinberg@tiho-hannover.de.
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D002853:Chromatography, Liquid; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007093:Imidazoles / Q000378:metabolism* / Q000633:toxicity; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D007700:Kinetics; D008297:Male; D011916:Rats, Inbred F344; D012307:Risk Factors; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002273:Carcinogens; D007093:Imidazoles; D016264:Dextran Sulfate; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
keywords: 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; Chronic colitis; Colorectal cancer; Dextran sulphate sodium; Heterocyclic aromatic amines; Ussing chamber