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

  • Toxicokinetics and Metabolism
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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.

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Acknowledgments

We thank Marion Burmester, Petra Nehrig and Alexandra Harder for their excellent technical assistance and Martin Beyerbach for his advice concerning the statistical analysis of the data.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany

    Petra Nicken, Anne von Keutz, Ina Willenberg, Annika I. Ostermann, Nils Helge Schebb & Pablo Steinberg

  2. Institute of Food Chemistry, University of Wuppertal, 42119, Wuppertal, Germany

    Nils Helge Schebb

  3. Department of Veterinary Pathology, Freie Universität Berlin, 14163, Berlin, Germany

    Samoa Giovannini & Olivia Kershaw

  4. Department of Physiology, University of Veterinary Medicine Hannover, Foundation, 30173, Hannover, Germany

    Gerhard Breves

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  1. Petra Nicken
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  2. Anne von Keutz
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  3. Ina Willenberg
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  4. Annika I. Ostermann
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  5. Nils Helge Schebb
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  9. Pablo Steinberg
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Correspondence to Pablo Steinberg.

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Nicken, P., von Keutz, A., Willenberg, I. et al. Impact of dextran sulphate sodium-induced colitis on the intestinal transport of the colon carcinogen PhIP. Arch Toxicol 90, 1093–1102 (2016). https://doi.org/10.1007/s00204-015-1546-1

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  • DOI: https://doi.org/10.1007/s00204-015-1546-1

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