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High Zinc Concentrations in Culture Media Affect Copper Uptake and Transport in Differentiated Human Colon Adenocarcinoma Cells^1,2,3,

U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034

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 µmol/L) in the culture and assay media on ⁶⁷Cu uptake and transport. Differentiated cells incubated for 7 d in a culture medium containing 50 µmol zinc + 0.7 µmol copper/L transported significantly less ⁶⁷Cu across the monolayer than similar cells exposed to 6 µmol zinc/L. However, cells exposed to 200 µmol zinc/L for the same period transported significantly more ⁶⁷Cu than those exposed to 6 µmol zinc/L. Cells exposed for only 1 h to 200 µmol 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 µmol zinc/L had higher cellular metallothionein (MT) than those exposed to 6 µmol zinc/L. As the amount of MT in cells increased upon exposure to 50 and 100 µmol 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.

KEY WORDS: • Caco-2 cells • copper-zinc interaction • copper-cadmium interaction • metallothionein • transport

¹ Presented in part at Experimental Biology 93, April 1993, New Orleans, LA [Briske-Anderson, M. & Reeves, P. G. (1993) Effect of zinc pretreatment on copper uptake and transport in Caco-2 cells. FASEB J. 7: A736 (abs.)] and Experimental Biology 94, April 1994, Anaheim, CA [Briske-Anderson, M., Newman, S. M., Jr., Idso, J. P., Finley, J. W. & Reeves, P. G. (1994) Culture conditions and passage number influence morphology and metabolism of Caco-2 cells. FASEB J. 8: A935 (abs.)].

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ Mention of a trademark or proprietary product does not constitute a guarantee of warranty of the product by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.

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Manuscript received 18 August 1995. Revision accepted 29 February 1996.