Archives of Toxicology

, Volume 90, Issue 5, pp 1093–1102 | Cite as

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

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 

References

  1. Bleich EM, Martin M, Bleich A, Klos A (2010) The Mongolian gerbil as a model for inflammatory bowel disease. Int J Exp Pathol 91:281–287CrossRefPubMedPubMedCentralGoogle Scholar
  2. Breves G, Walter C, Burmester M, Schröder B (2000) In vitro studies on the effects of Saccharomyces boulardii and Bacillus cereus var. toyoi on nutrient transport in pig jejunum. J Anim Physiol Anim Nutr 84:9–20CrossRefGoogle Scholar
  3. Camuesco D, Comalada M, Concha A, Nieto A, Sierra S, Xaus J, Zarzuelo A, Gálvez J (2006) Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis. Clin Nutr 25:466–476CrossRefPubMedGoogle Scholar
  4. Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD, Rodriguez C, Sinha R, Calle EE (2005) Meat consumption and risk of colorectal cancer. JAMA 293:172–182CrossRefPubMedGoogle Scholar
  5. Clapper ML, Cooper HS, Chang WC (2007) Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions. Acta Pharmacol Sin 28:1450–1459CrossRefPubMedGoogle Scholar
  6. Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249PubMedGoogle Scholar
  7. Corridoni D, Arseneau KO, Cominelli F (2014) Inflammatory bowel disease. Immunol Lett 161:231–235CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cross AJ, Ferrucci LM, Risch A, Graubard BI, Ward MH, Park Y, Hollenbeck AR, Schatzkin A, Sinha R (2010) A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res 70:2406–2414CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dietrich CG, de Waart DR, Ottenhoff R, Schoots IG, Elferink RP (2001) Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in MRP2-deficient rats. Mol Pharmacol 59:974–980PubMedGoogle Scholar
  10. Dingley KH, Curtis KD, Nowell S, Felton JS, Lang NP, Turteltaub KW (1999) DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Epidemiol Biomark Prev 8:507–512Google Scholar
  11. Doi K, Wanibuchi H, Salim EI, Morimura K, Kinoshita A, Kudoh S, Hirata K, Yoshikawa J, Fukushima S (2005) Lack of large intestinal carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine at low doses in rats initiated with azoxymethane. Int J Cancer 115:870–878CrossRefPubMedGoogle Scholar
  12. Dragsted LO, Frandsen H, Reistad R, Alexander J, Larsen JC (1995) DNA-binding and disposition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat. Carcinogenesis 16:2785–2793CrossRefPubMedGoogle Scholar
  13. Fernandez-Blanco JA, Barbosa S, Sanchez de Medina F, Martinez V, Vergara P (2011) Persistent epithelial barrier alterations in a rat model of postinfectious gut dysfunction. Neurogastroenterol Motil 23:e523–e533CrossRefPubMedGoogle Scholar
  14. Frandsen H, Grivas S, Andersson R, Dragsted L, Larsen JC (1992) Reaction of the N 2-acetoxy derivative of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) with 2′-deoxyguanosine and DNA. Synthesis and identification of N 2-(2′-deoxyguanosin-8-yl)-PhIP. Carcinogenesis 13:629–635CrossRefPubMedGoogle Scholar
  15. Friesen MD, Kaderlik K, Lin D, Garren L, Bartsch H, Lang NP, Kadlubar FF (1994) Analysis of DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in rat and human tissues by alkaline hydrolysis and gas chromatography/electron capture mass spectrometry: validation by comparison with 32P-postlabeling. Chem Res Toxicol 7:733–739CrossRefPubMedGoogle Scholar
  16. Fukushima S, Wanibuchi H, Morimura K, Iwai S, Nakae D, Kishida H, Tsuda H, Uehara N, Imaida K, Shirai T, Tatematsu M, Tsukamoto T, Hirose M, Furukawa F (2004) Existence of a threshold for induction of aberrant crypt foci in the rat colon with low doses of 2-amino-1-methyl-6-phenolimidazo[4,5-b]pyridine. Toxicol Sci 80:109–114CrossRefPubMedGoogle Scholar
  17. Gassler N, Rohr C, Schneider A, Kartenbeck J, Bach A, Obermüller N, Otto HF, Autschbach F (2001) Inflammatory bowel disease is associated with changes of enterocytic junctions. Am J Physiol 281:G216–G228Google Scholar
  18. Hasegawa R, Sano M, Tamano S, Imaida K, Shirai T, Nagao M, Sugimura T, Ito N (1993) Dose-dependence of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) carcinogenicity in rats. Carcinogenesis 14:2553–2557CrossRefPubMedGoogle Scholar
  19. Ito N, Hasegawa R, Sano M, Tamano S, Esumi H, Takayama S, Sugimura T (1991) A new colon and mammary carcinogen in cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Carcinogenesis 12:1503–1506CrossRefPubMedGoogle Scholar
  20. Janakiram NB, Rao CV (2014) The role of inflammation in colon cancer. Adv Exp Med Biol 816:25–52CrossRefPubMedGoogle Scholar
  21. Kühnel D, Taugner F, Scholtka B, Steinberg P (2009) Inflammation does not precede or accompany the induction of preneoplastic lesions in the colon of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-fed rats. Arch Toxicol 83:763–768CrossRefPubMedGoogle Scholar
  22. Kullmann F, Messmann H, Alt M, Gross V, Bocker T, Schölmerich J, Rüschoff J (2001) Clinical and histopathological features of dextran sulfate sodium induced acute and chronic colitis associated with dysplasia in rats. Int J Colorectal Dis 16:238–246CrossRefPubMedGoogle Scholar
  23. Layton DW, Bogen KT, Knize MG, Hatch FT, Johnson VM, Felton JS (1995) Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research. Carcinogenesis 16:39–52CrossRefPubMedGoogle Scholar
  24. Mähler M, Bristol IJ, Leiter EH, Workman AE, Birkenmeier EH, Elson CO, Sundberg JP (1998) Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am J Physiol 274:G544–G551PubMedGoogle Scholar
  25. Malfatti MA, Dingley KH, Nowell-Kadlubar S, Ubick EA, Mulakken N, Nelson D, Lang NP, Felton JS, Turteltaub KW (2006) The urinary metabolite profile of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is predictive of colon DNA adducts after a low-dose exposure in humans. Cancer Res 66:10541–10547CrossRefPubMedGoogle Scholar
  26. Nakanishi M, Tazawa H, Tsuchiya N, Sugimura T, Tanaka T, Nakagama H (2007) Mouse strain differences in inflammatory responses of colonic mucosa induced by dextran sulfate sodium cause differential susceptibility to PhIP-induced large bowel carcinogenesis. Cancer Sci 98:1157–1163CrossRefPubMedGoogle Scholar
  27. Nicken P, Hamscher G, Breves G, Steinberg P (2010) Uptake of the colon carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by different segments of the rat gastrointestinal tract: its implication in colorectal carcinogenesis. Toxicol Lett 196:60–66CrossRefPubMedGoogle Scholar
  28. Nicken P, Schröder B, von Keutz A, Breves G, Steinberg P (2013) The colon carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is actively secreted in the distal colon of the rat: an integrated view on the role of PhIP transport and metabolism in PhIP-induced colon carcinogenesis. Arch Toxicol 87:895–904CrossRefPubMedGoogle Scholar
  29. Nishikawa A, Imazawa T, Kuroiwa Y, Kitamura Y, Kanki K, Ishii Y, Umemura T, Hirose M (2005) Induction of colon tumors in C57BL/6J mice fed MeIQx, IQ, or PhIP followed by dextran sulfate sodium treatment. Toxicol Sci 84:243–248CrossRefPubMedGoogle Scholar
  30. Norat T, Bingham S, Ferrari P, Slimani N, Jenab M, Mazuir M, Overvad K, Olsen A, Tjønneland A, Clavel F, Boutron-Ruault MC, Kesse E, Boeing H, Bergmann MM, Nieters A, Linseisen J, Trichopoulou A, Trichopoulos D, Tountas Y, Berrino F, Palli D, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Engeset D, Lund E, Skeie G, Ardanaz E, González C, Navarro C, Quirós JR, Sanchez MJ, Berglund G, Mattisson I, Hallmans G, Palmqvist R, Day NE, Khaw KT, Key TJ, San Joaquin M, Hémon B, Saracci R, Kaaks R, Riboli E (2005) Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. J Natl Cancer Inst 97:906–916CrossRefPubMedPubMedCentralGoogle Scholar
  31. Perse M, Cerar A (2012) Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol 2012:718617CrossRefPubMedPubMedCentralGoogle Scholar
  32. Rachmilewitz D, Karmeli F, Takabayashi K, Hayashi T, Leider-Trejo L, Lee J, Leoni LM, Raz E (2002) Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology 122:1428–1441CrossRefPubMedGoogle Scholar
  33. Rohrmann S, Zoller D, Hermann S, Linseisen J (2007) Intake of heterocyclic aromatic amines from meat in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort. Br J Nutr 98:1112–1115CrossRefPubMedGoogle Scholar
  34. Salim SY, Soderholm JD (2011) Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis 17:362–381CrossRefPubMedGoogle Scholar
  35. Schut HA, Herzog CR (1992) Formation of DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in male Fischer-344 rats. Cancer Lett 67:117–124CrossRefPubMedGoogle Scholar
  36. Shioya M, Wakabayashi K, Sato S, Nagao M, Sugimura T (1987) Formation of a mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) in cooked beef, by heating a mixture containing creatinine, phenylalanine and glucose. Mutat Res 191:133–138CrossRefPubMedGoogle Scholar
  37. Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212–236CrossRefPubMedGoogle Scholar
  38. Sullivan KM, Erickson MA, Sandusky CB, Barnard ND (2008) Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California. Nutr Cancer 60:592–602CrossRefPubMedGoogle Scholar
  39. Tanaka T, Suzuki R, Kohno H, Sugie S, Takahashi M, Wakabayashi K (2005) Colonic adenocarcinomas rapidly induced by the combined treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate in male ICR mice possess β-catenin gene mutations and increases immunoreactivity for β-catenin, cyclooxygenase-2 and inducible nitric oxide synthase. Carcinogenesis 26:229–238CrossRefPubMedGoogle Scholar
  40. Thompson LH, Tucker JD, Stewart SA, Christensen ML, Salazar EP, Carrano AV, Felton JS (1987) Genotoxicity of compounds from cooked beef in repair-deficient CHO cells versus Salmonella mutagenicity. Mutagenesis 2:483–487CrossRefPubMedGoogle Scholar
  41. Tóth B, Leonhard-Marek S, Hedrich HJ, Breves G (2008) Characterization of electrogenic nutrient absorption in the CftrTgH(neoim)Hgu mouse model. J Comp Physiol B 178:705–712CrossRefPubMedGoogle Scholar
  42. Ussing HH, Zerhahn K (1951) Active transport of sodium as the source of electric current in the short-circuited isolated frog skin. Acta Physiol Scand 23:110–127CrossRefPubMedGoogle Scholar
  43. van Herwaarden AE, Jonker JW, Wagenaar E, Brinkhuis RF, Schellens JH, Beijnen JH, Schinkel AH (2003) The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res 63:6447–6452PubMedGoogle Scholar
  44. Walle UK, Walle T (1999) Transport of the cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) across the human intestinal Caco-2 cell monolayer: role of efflux pumps. Carcinogenesis 20:2153–2157CrossRefPubMedGoogle Scholar
  45. Willenberg I, von Elsner L, Steinberg P, Schebb NH (2015) Development of an online-SPE-LC-MS method for the investigation of the intestinal absorption of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) and its bacterial metabolite PHIP-M1 in a Caco-2 Transwell system. Food Chem 166:537–543CrossRefPubMedGoogle Scholar

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

Personalised recommendations