title: Intestinal transport and metabolism of acrylamide.
abstract: There has been an intensive debate whether dietary exposure to acrylamide could increase the risk of human cancer since the first description of the presence of acrylamide in food in 2002. As the intestinal mechanisms of acrylamide absorption are poorly investigated we studied the transport of acrylamide in differentiated Caco-2 cells and its effects on biotransformation enzymes (CYP2E1 and glutathione S-transferase) and glutathione levels. We found that the apparent permeability of [1-(14)C] acrylamide from the basal to the apical compartment was approximately 20% higher compared to that in the opposite direction. No differences were detected for apical-basal transport against a basal gradient. Transport rates from the apical to the basal chamber at 4 degrees C were about 50% lower than at 37 degrees C. Concentration dependent transport from apical to basal was linear. Predominantly, basal to apical transport was decreased when energy metabolism of the cells was inhibited by application of sodium azide and 2-deoxy-d-glucose. Finally, more acrylamide was transported at luminal pH 6 compared to pH 7.4 from basal to the apical direction. Increasing levels of acrylamide showed no effects on the activity of glutathione S-transferase but resulted in a depletion of total glutathione concentrations. In conclusion transport of acrylamide in the intestine is mediated primarily by passive processes possibly combined with a modest energy- and pH-dependent active secretory component. Depletion of cellular glutathione levels may be one potential mechanism for acrylamide (geno)toxicity.
authors.affiliation: Department of Physiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Zödl
authors.forename: Diethart
authors.initials: D
authors.lastname: Schmid
authors.forename: Georg
authors.initials: G
authors.lastname: Wassler
authors.forename: Claudia
authors.initials: C
authors.lastname: Gundacker
authors.forename: Valentin
authors.initials: V
authors.lastname: Leibetseder
authors.forename: Theresia
authors.initials: T
authors.lastname: Thalhammer
authors.forename: Cem
authors.initials: C
authors.lastname: Ekmekcioglu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D020106:Acrylamide / Q000493:pharmacokinetics* / Q000633:toxicity; D001692:Biological Transport; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D019810:Sodium Azide / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D020106:Acrylamide; D008353:Mannitol; D019810:Sodium Azide; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D005978:Glutathione