Impact of dextran sulphate sodium-induced colitis on the intestinal transport of the colon carcinogen PhIP

• Published in: Archives of toxicology Vol. 90; no. 5; pp. 1093 - 1102
• Main Authors: Nicken, Petra, von Keutz, Anne, Willenberg, Ina, Ostermann, Annika I., Schebb, Nils Helge, Giovannini, Samoa, Kershaw, Olivia, Breves, Gerhard, Steinberg, Pablo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2016
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Carcinogens - metabolism; Carcinogens - toxicity; Chromatography, Liquid; Chronic Disease; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Colonic Neoplasms - chemically induced; Colonic Neoplasms - metabolism; Dextran Sulfate; Disease Models, Animal; Environmental Health; Imidazoles - metabolism; Imidazoles - toxicity; Intestinal Absorption; Intestinal Mucosa - metabolism; Intestines - metabolism; Intestines - pathology; Kinetics; Male; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Rats, Inbred F344; Risk Factors; Spectrometry, Mass, Electrospray Ionization; Toxicokinetics and Metabolism; Dextran sulphate sodium; Chronic colitis; Colorectal cancer; pyridine; Ussing chamber; 2-Amino-1-methyl-6-phenylimidazo[4,5; Heterocyclic aromatic amines; 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-015-1546-1

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.