title: High zinc concentrations in culture media affect copper uptake and transport in differentiated human colon adenocarcinoma cells.
abstract: Previous studies suggest that high dietary zinc reduces the copper status of animals by reducing copper transport across the intestinal mucosa. The present study used an enterocyte mimic, the Caco-2 cell, grown on porus membranes as a model to assess the effects of various concentrations of zinc (6 to 200 micromol/L) in the culture and assay media on 67Cu uptake and transport. Differentiated cells incubated for 7 d in a culture medium containing 50 micromol zinc + 0.7 micromol copper/L transported significantly less 67Cu across the monolayer than similar cells exposed to 6 micromol zinc/L. However, cells exposed to 200 micromol zinc/L for the same period transported significantly more 67Cu than those exposed to 6 micromol zinc/L. Cells exposed for only 1 h to 200 micromol zinc/L in the uptake-transport medium alone did not show lower 67Cu uptake or transport, suggesting that time of exposure of the cells to high zinc was a contributing factor. Caco-2 cells exposed to 50 through 200 micromol zinc/L had higher cellular metallothionein (MT) than those exposed to 6 micromol zinc/L. As the amount of MT in cells increased upon exposure to 50 and 100 micromol zinc/L, the rate of 67Cu transport decreased. At higher zinc concentrations in the medium, there was even more MT in the cells, but a greater rate Of 67Cu transport. These studies demonstrate the use of the Caco-2 cell as a model for copper uptake-transport studies, but the conditions must be rigorously defined and controlled.
authors.affiliation: U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Reeves
authors.forename: M
authors.initials: M
authors.lastname: Briske-Anderson
authors.forename: S M
authors.initials: SM
authors.lastname: Newman
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002104:Cadmium / Q000494:pharmacology; D002454:Cell Differentiation; D003300:Copper / Q000378:metabolism*; D003301:Copper Radioisotopes; D003470:Culture Media; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D003301:Copper Radioisotopes; D003470:Culture Media; D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D015032:Zinc