Archives of Toxicology

, Volume 90, Issue 5, pp 1093–1102

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

  • Petra Nicken
  • Anne von Keutz
  • Ina Willenberg
  • Annika I. Ostermann
  • Nils Helge Schebb
  • Samoa Giovannini
  • Olivia Kershaw
  • Gerhard Breves
  • Pablo Steinberg
Toxicokinetics and Metabolism

DOI: 10.1007/s00204-015-1546-1

Cite this article as:
Nicken, P., von Keutz, A., Willenberg, I. et al. Arch Toxicol (2016) 90: 1093. doi:10.1007/s00204-015-1546-1

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.

Keywords

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Chronic colitis Colorectal cancer Dextran sulphate sodium Heterocyclic aromatic amines Ussing chamber 

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Petra Nicken
    • 1
  • Anne von Keutz
    • 1
  • Ina Willenberg
    • 1
  • Annika I. Ostermann
    • 1
  • Nils Helge Schebb
    • 1
    • 2
  • Samoa Giovannini
    • 3
  • Olivia Kershaw
    • 3
  • Gerhard Breves
    • 4
  • Pablo Steinberg
    • 1
  1. 1.Institute for Food Toxicology and Analytical ChemistryUniversity of Veterinary Medicine Hannover, FoundationHannoverGermany
  2. 2.Institute of Food ChemistryUniversity of WuppertalWuppertalGermany
  3. 3.Department of Veterinary PathologyFreie Universität BerlinBerlinGermany
  4. 4.Department of PhysiologyUniversity of Veterinary Medicine Hannover, FoundationHannoverGermany