Journal article

Publication year: 2015

Pages: 92-98

Journal: Toxicology Letters

Volume number: 234

Issue number: 2

ISSN: 0378-4274

DOI Link: https://doi.org/10.1016/j.toxlet.2015.02.015

Publisher: Elsevier

Abstract: 
Previous studies have shown that in the rat, the colon carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is only absorbed to a limited extent in the small intestines and that a major fraction of unmetabolised PhIP reaches the colon. Moreover, PhIP is extensively metabolised when incubated with human stool samples to a major derivative, 7-hydroxy-5-methyl-3-phenyl-6,7,8,9-tetrahydropyrido [3',2':4,5]imidazo[1,2-a]pyrimidin-5-ium chloride (PhIP-M1). In the present study, the uptake and transport of PhIP-M1 in Ussing chamber experiments, its cytotoxicity in the different segments of the Fischer 344 rat gut and its transforming potential in the BALB/c 3T3 cell transformation assay were analysed. At the most, 10-20% of the PhIP-M1 amount added to the mucosal compartment of the Ussing chambers per segment were absorbed within 90min. Therefore, the amount of PhIP-M1 detected in the tissues as well as in the serosal compartment of the Ussing chambers was extremely low. Moreover, human-relevant concentrations of PhIP-M1 were not cytotoxic and did not induce the malignant transformation of BALB/c 3T3 cells. In conclusion, even if one would assume that 100% of the daily amount of PhIP ingested by a human being is converted into PhIP-M1 in the colon, this concentration most probably would not lead to cytotoxicity and/or carcinogenicity in the colorectal mucosa.

Harvard Citation style: Nicken, P., Willenberg, I., von Keutz, A., von Elsner, L., Hamscher, G., Vanhaecke, L., et al. (2015) Intestinal absorption and cell transforming potential of PhIP-M1, a bacterial metabolite of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), Toxicology Letters, 234(2), pp. 92-98. https://doi.org/10.1016/j.toxlet.2015.02.015

APA Citation style: Nicken, P., Willenberg, I., von Keutz, A., von Elsner, L., Hamscher, G., Vanhaecke, L., Schroder, B., Breves, G., Schebb, N., & Steinberg, P. (2015). Intestinal absorption and cell transforming potential of PhIP-M1, a bacterial metabolite of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Toxicology Letters. 234(2), 92-98. https://doi.org/10.1016/j.toxlet.2015.02.015