| 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. | |
| | |
MedLine Citation:
|
PMID: 10545419 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Cooked-food mutagens formed when frying meat have been suggested to contribute to the etiology of colon, breast and prostate cancer. The most prevalent of these mutagens is 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which after absorption is bioactivated by both phase I and phase II enzymes. Although available data suggest absorption of PhIP in humans, the extent and mechanism of absorption are unknown. In the present study we examined the transport of [(3)H]PhIP through the human Caco-2 intestinal epithelial cell monolayer, a well-accepted model of human intestinal absorption. The influx, or absorption, was extensive and linear for 2 h and up to a PhIP concentration of 5 microM. Still, the basolateral to apical efflux [apparent permeability coefficient (P(app)) 54.2 +/- 0.7x10(-6) cm/s, mean +/- SEM, n = 24] was 3.6 times greater than the apical to basolateral influx (P(app) 15.1 +/- 0.6x10(-6) cm/s, n = 21, P < 0.0001). Equilibrium exchange experiments demonstrated the efflux to be a true active process. Preincubations with verapamil, an inhibitor of P-glycoprotein-mediated transport, or MK-571, an inhibitor of multidrug resistance-associated protein-mediated transport, stimulated influx and reduced efflux of PhIP, suggesting that PhIP is a substrate for both of these transporters. These findings should be considered when determining exposure to the cooked food mutagens. |
| | |
Authors:
|
U K Walle; T Walle |
Related Documents
:
|
785249 - Mutagenic actions of chlorocholine chloride. 12505279 - Food and cancer. 2558079 - Volatile nitrosamine levels and genotoxicity of food samples from high-risk areas for n... 11038239 - Excretion of volatile nitrosamines in a rural population in relation to food and drinki... 8436429 - Dietary carcinogens and the risk for glioma and meningioma in germany. 3530739 - Mutagen formation during commercial processing of foods. 16928099 - Selective synthesis of functionalized thia- and oxacalix[2]arene[2]pyrimidines. 19735199 - Is norovirus a foodborne or pandemic pathogen? an analysis of the transmission of norov... 20349839 - Understanding long-term primate community dynamics: implications of forest change. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Carcinogenesis Volume: 20 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 1999 Nov |
Date Detail:
|
Created Date: 2000-01-03 Completed Date: 2000-01-03 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: ENGLAND |
Other Details:
|
Languages: eng Pagination: 2153-7 Citation Subset: IM |
Affiliation:
|
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Biological Transport Caco-2 Cells Food* Humans Imidazoles / pharmacokinetics* Intestines / cytology, metabolism* Mutagens / pharmacokinetics* P-Glycoprotein / antagonists & inhibitors Verapamil / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
|
CA69138/CA/NCI NIH HHS; GM55561/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Imidazoles; 0/Mutagens; 0/P-Glycoprotein; 105650-23-5/2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; 52-53-9/Verapamil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Heterocyclic aromatic amines efficiently induce mitotic recombination in metabolically competent Sac...
Next Document: Strain-dependent lung tumor formation in mice transplacentally exposed to 3-methylcholanthrene and p...