Skip to main content
SpringerLink
Log in

Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a long-term Caco-2 TC7 cell model

  • Published:
Biometals Aims and scope Submit manuscript

Abstract

The influence of long-term exposure to cadmium (Cd) on essential minerals was investigated using a Caco-2 TC7 cells and a multi-analytical tool: microwave digestion and inductively coupled plasma mass spectrometry. Intracellular levels, effects on cadmium accumulation, distribution, and reference concentration ranges of the following elements were determined: Na, Mg, Ca, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mo, and Cd. Results showed that Caco-2 TC7 cells incubated long-term with cadmium concentrations ranging from 0 to 10 μmol Cd/l for 5 weeks exhibited a significant increase in cadmium accumulation. Furthermore, this accumulation was more marked in cells exposed long-term to cadmium compared with controls, and that this exposure resulted in a significant accumulation of copper and zinc but not of the other elements measured. Interactions of Cd with three elements: zinc, copper, and manganese were particularly studied. Exposed to 30 μmol/l of the element, manganese showed the highest inhibition and copper the lowest on cadmium intracellular accumulation but Zn, Cu, and Mn behave differently in terms of their mutual competition with Cd. Indeed, increasing cadmium in the culture medium resulted in a gradual and significant increase in the accumulation of zinc. There was a significant decrease in manganese from 5 μmol Cd/l exposure, and no variation was observed with copper.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AAS:

Atomic absorption spectrometry

CRM:

Certified reference material

PBS:

Phosphate buffered saline without calcium and magnesium

DMEM:

Dubelcco’s modified Eagle’s medium

References

  • T Alfven L Jarup CG Elinder (2002) ArticleTitleCadmium and lead in blood in relation to low bone mineral density and tubular proteinuria Environ Health Persp 110 699–702 Occurrence Handle1:CAS:528:DC%2BD38XmvFSntbY%3D Occurrence Handle10.1289/ehp.02110699

    Article  CAS  Google Scholar 

  • RM Barnes (1993) ArticleTitleAdvances in inductively coupled plasma mass spectrometry: human nutrition and toxicology Anal Chim Acta 283 115–130 Occurrence Handle1:CAS:528:DyaK2cXivFyksg%3D%3D Occurrence Handle10.1016/0003-2670(93)85214-5

    Article  CAS  Google Scholar 

  • A Blais S Lecoeur (1999) ArticleTitleCadmium uptake and transepithelial transport in control and long-term exposed Caco-2 cells: the role of metallothionein Toxicol Appl Pharmacol 160 76–85 Occurrence Handle10502504 Occurrence Handle1:CAS:528:DyaK1MXmt1Wqurg%3D Occurrence Handle10.1006/taap.1999.8735

    Article  PubMed  CAS  Google Scholar 

  • A Blais S Lecoeur G Milhaud D Tome M Kolf-Clauw (1999) ArticleTitleCadmium uptake and transepithelial transport in control and long-term exposed Caco-2 cells: the role of metallothionein Toxicol Appl Pharmacol 160 76–85 Occurrence Handle10502504 Occurrence Handle1:CAS:528:DyaK1MXmt1Wqurg%3D Occurrence Handle10.1006/taap.1999.8735

    Article  PubMed  CAS  Google Scholar 

  • ME Blazka ZA Shaikh (1992) ArticleTitleCadmium and mercury accumulation in rat hepatocytes: interactions with other metal ions Toxicol Appl Pharmacol 113 118–125 Occurrence Handle1553744 Occurrence Handle1:CAS:528:DyaK38XitV2hurY%3D Occurrence Handle10.1016/0041-008X(92)90015-K

    Article  PubMed  CAS  Google Scholar 

  • M Boveri P Pazos A Genari J Casado T Hartung P Prieto (2004) ArticleTitleComparison of the sensitivity of different toxicological endpoints in Caco-2 cells after cadmium chloride treatment Arch Toxicol 78 201–206 Occurrence Handle14661071 Occurrence Handle1:CAS:528:DC%2BD2cXjtVWltrk%3D Occurrence Handle10.1007/s00204-003-0532-1

    Article  PubMed  CAS  Google Scholar 

  • MM Brzoska J Moniuszko-Jakoniuk (2001) ArticleTitleInteractions between cadmium and zinc in the organism Food Chem Toxicol 39 967–980 Occurrence Handle11524135 Occurrence Handle1:CAS:528:DC%2BD3MXmt1Oqu7c%3D Occurrence Handle10.1016/S0278-6915(01)00048-5

    Article  PubMed  CAS  Google Scholar 

  • RL Chaney PG Reeves JS Angle (2001) Rice plant nutritional and human nutritional characteristics roles in human Cd toxicity WJ Horst (Eds) Plant Nutrition: Food Security and Sustainability of Agro-ecosystems through Basic and Applied Research Germany Dordrecht 228–289

    Google Scholar 

  • I Chantret A Rodolosse A Barbat E Dussaulx E Brot-Laroche A Zweibaum M Rousset (1994) ArticleTitleDifferential expression of sucrase-isomaltase in clones isolated from early and late passages of the cell line Caco-2: evidence for glucose-dependent negative regulation J Cell Sci 107 213–225 Occurrence Handle8175910 Occurrence Handle1:CAS:528:DyaK2cXis1KktLY%3D

    PubMed  CAS  Google Scholar 

  • NT Davies JK Campbell (1977) ArticleTitleThe effect of cadmium on intestinal copper absorption and binding in the rat Life Sci 20 955–960 Occurrence Handle850464 Occurrence Handle1:CAS:528:DyaE2sXhs12lsrY%3D Occurrence Handle10.1016/0024-3205(77)90281-8

    Article  PubMed  CAS  Google Scholar 

  • F Delie W Rubas (1997) ArticleTitleA human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model Crit Rev Therap Drug Carrier Syst 14 221–286 Occurrence Handle1:CAS:528:DyaK2sXlvFeru7c%3D

    CAS  Google Scholar 

  • G Eklund A Lindén J Tallkvist A Oskarsson (2003) ArticleTitleBioavailability of cadmium from in vitro digested infant food studied in Caco-2 cells J Agric Food Chem 51 4168–4174 Occurrence Handle12822963 Occurrence Handle1:CAS:528:DC%2BD3sXktl2jsrw%3D Occurrence Handle10.1021/jf0343884

    Article  PubMed  CAS  Google Scholar 

  • T Endo O Kimura M Sakata (1996) ArticleTitleEffects of zinc and copper on uptake of cadmium by LLC-PK1 cells Biol Pharm Bull 19 944–948 Occurrence Handle8839966 Occurrence Handle1:CAS:528:DyaK28XksVGju7k%3D

    PubMed  CAS  Google Scholar 

  • S Ferruzza Y Sambuy MR Ciriolo A De Martino P Santaroni G Rotilio ML Scarino (2000) ArticleTitleCopper uptake and intracellular distribution in the human intestinal Caco-2 cell line BioMetals 13 179–185 Occurrence Handle11016407 Occurrence Handle1:CAS:528:DC%2BD3cXmvFKis7Y%3D Occurrence Handle10.1023/A:1009271622356

    Article  PubMed  CAS  Google Scholar 

  • Finley JW, Briske-Anderson M, Reeves PG, Johnson LK. 1995 Zinc uptake and transcellular movement by caco-2 cells: studies with media containing fetal bovine serum. Nutr Biochem, 137–144

  • J Fogh JM Fogh T Orfeo (1977) ArticleTitleOne hundred and twenty seven cultured human tumor cell lines producing tumors in nude mice J Natl Cancer Inst 59 221–226 Occurrence Handle327080 Occurrence Handle1:STN:280:DyaE2s3htVSgtg%3D%3D

    PubMed  CAS  Google Scholar 

  • L Friberg T Kjerström GF Norberg (1986) Cadmium L Friberg GF Norberg V Vouk (Eds) Handbook on the Toxicology of Metals Elsevier Science Publishers B.V. Amsterdam 131–183

    Google Scholar 

  • B Gachot P Poujeol (1992) ArticleTitleEffects of cadmium and copper on zinc transport kinetics by isolated renal proximal cells Biol Trace Element Res 35 93–103 Occurrence Handle1:CAS:528:DyaK3sXhslKnsw%3D%3D

    CAS  Google Scholar 

  • IJ Hidalgo TJ Raub RT Borchardt (1989) ArticleTitleCharacterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability Gastroenterology 96 736–749 Occurrence Handle2914637 Occurrence Handle1:STN:280:DyaL1M7itFeqsg%3D%3D

    PubMed  CAS  Google Scholar 

  • P Houpert B Federspiel G Milhaud (1997) ArticleTitleToxicokinetics of cadmium in lactating and nonlactating ewes after oral and intravenous administration Environ Res 72 140–150 Occurrence Handle9177656 Occurrence Handle1:CAS:528:DyaK2sXislGltLw%3D Occurrence Handle10.1006/enrs.1996.3690

    Article  PubMed  CAS  Google Scholar 

  • C Huynh-Delerme H Huet L Noel A Frigieri M Kolf-Clauw (2005) ArticleTitleIncreased functional expression of P-glycoprotein in Caco-2 TC7 cells exposed long-term to cadmium Toxicol In Vitro 19 439–447 Occurrence Handle15826803 Occurrence Handle1:CAS:528:DC%2BD2MXjtF2jsL4%3D Occurrence Handle10.1016/j.tiv.2004.08.003

    Article  PubMed  CAS  Google Scholar 

  • M Jovani R Barbera R Farre E Martin De Aguilera (2001) ArticleTitleCalcium, iron, and zinc uptake from digests of infant formulas by caco-2 cells J Agric Food Chem 49 3480–3485 Occurrence Handle11453795 Occurrence Handle1:CAS:528:DC%2BD3MXksVars7o%3D Occurrence Handle10.1021/jf010106t

    Article  PubMed  CAS  Google Scholar 

  • C Jumarie PG Campbell M Houde F Denizeau (1999) ArticleTitleEvidence for an intracellular barrier to cadmium transport through Caco-2 cell monolayers J Cell Physiol 180 285–297 Occurrence Handle10395298 Occurrence Handle1:CAS:528:DyaK1MXkt1CjtrY%3D Occurrence Handle10.1002/(SICI)1097-4652(199908)180:2<285::AID-JCP16>3.0.CO;2-3

    Article  PubMed  CAS  Google Scholar 

  • C Jumarie PGC Campbell A Berteloot M Houde F Denizeau (1997) ArticleTitleCaco-2 cell line used as an in vitro model to study cadmium accumulation in intestinal epithelial cells J Membrane Biol 158 31–48 Occurrence Handle1:CAS:528:DyaK2sXksF2ks7w%3D Occurrence Handle10.1007/s002329900241

    Article  CAS  Google Scholar 

  • E Le Ferrec C Chesne P Artusson D Brayden G Fabre P Gires F Guillou M Rousset W Rubas ML Scarino (2001) ArticleTitleIn Vitro Models of the Intestinal Barrier ATLA 29 649–668 Occurrence Handle11709041 Occurrence Handle1:STN:280:DC%2BD3MnmtleksA%3D%3D

    PubMed  CAS  Google Scholar 

  • L Mata L Sanchez M Calvo (1996) ArticleTitleCadmium uptake by Caco-2 cells. Effect of some milk components Chem Biol Interact 100 277–288 Occurrence Handle8653809 Occurrence Handle1:CAS:528:DyaK28XjtFarur4%3D Occurrence Handle10.1016/0009-2797(96)03706-4

    Article  PubMed  CAS  Google Scholar 

  • L Noël T Guérin JM Frémy H Huet M Kolf-Clauw (2003a) ArticleTitleOptimized simultaneous determination of several elements in human intestinal Caco-2 TC7 cells by inductively coupled plasma-mass spectrometry after closed vessel microwave digestion J AOAC Int 86 1225–1231

    Google Scholar 

  • L Noël JC Leblanc T Guérin (2003b) ArticleTitleDetermination of several elements in duplicate meals from catering establishment using closed vessel microwave digestion with inductively coupled plasma mass spectrometry detection: estimation of daily dietary intake Food Additives Contaminants 20 IssueIDno. 1 44–56 Occurrence Handle10.1080/0265203021000031573

    Article  Google Scholar 

  • L Noël T Guérin M Kolf-Clauw (2004) ArticleTitleSubchronic dietary exposure of rats to cadmium alters the metabolism of metals essential to bone health Food Chem Toxicol 42 1203–1210 Occurrence Handle15207369 Occurrence Handle10.1016/j.fct.2004.02.017 Occurrence Handle1:CAS:528:DC%2BD2cXltVKitL0%3D

    Article  PubMed  CAS  Google Scholar 

  • C Orlowski JK Piotrowski (2003) ArticleTitleBiological levels of cadmium and zinc in the small intestine of non-occupationally exposed human subjects Human Exp Toxicol 22 57–63 Occurrence Handle1:CAS:528:DC%2BD3sXjt1yrtLo%3D Occurrence Handle10.1191/0960327103ht326oa

    Article  CAS  Google Scholar 

  • W Pfaller M Balls R Clothier S Coecke P Dierickx B Ekwall BA Hanley T Hartung P Prieto MP Ryan G Schmuck D Sladowski JA Vericat A Wendel A Wolf J Zimmer (2001) ArticleTitleNovel advanced in vitro methods for long-term toxicity testing – ECVAM Workshop Report Alternat Lab Anim 29 393–426 Occurrence Handle1:STN:280:DC%2BD3Mvmt1Sgug%3D%3D

    CAS  Google Scholar 

  • EA Pigman J Blanchard HE Laird SuffixII (1997) ArticleTitleA study of cadmium transport pathways using the Caco-2 cell model Toxicol Appl Pharmacol 142 243–247 Occurrence Handle9070345 Occurrence Handle1:CAS:528:DyaK2sXhsFaqtr0%3D Occurrence Handle10.1006/taap.1996.8039

    Article  PubMed  CAS  Google Scholar 

  • M Pinto S Robine-Leon MB Appay M Kedinger N Triadou E Dussaulx B Lacroix P Simon-Assman K Haffen J Fogh A Zweibaum (1983) ArticleTitleEnterocyte-like differenciation and polarization of the human colon carcinoma cell line Caco 2 in culture Biol Cell 47 323–330

    Google Scholar 

  • G Ranaldi R Consalvo Y Sambuy ML Scarino (2003) ArticleTitlePermeability characteristics of parental and clonal human intestinal Caco-2 cell lines differentiated in serum-supplemented and serum-free media Toxicol In Vitro 17 761–767 Occurrence Handle14599474 Occurrence Handle1:CAS:528:DC%2BD3sXos12ltro%3D Occurrence Handle10.1016/S0887-2333(03)00095-X

    Article  PubMed  CAS  Google Scholar 

  • PG Reeves M Briske-Anderson L Johnson (2001) ArticleTitlePre-treatment of Caco-2 cells with zinc during the differentiation phase alters the kinetics of zinc uptake and transport(2) J Nutr Biochem 12 674–684 Occurrence Handle12031250 Occurrence Handle1:CAS:528:DC%2BD3MXotFSqt78%3D Occurrence Handle10.1016/S0955-2863(01)00185-1

    Article  PubMed  CAS  Google Scholar 

  • PG Reeves M Briske-Anderson SM Newman SuffixJr (1996) ArticleTitleHigh zinc concentrations in culture media affect copper uptake and transport in differentiated human colon adenocarcinoma cells J Nutr 126 1701–1712 Occurrence Handle8648446 Occurrence Handle1:CAS:528:DyaK28XjtlKkt7g%3D

    PubMed  CAS  Google Scholar 

  • A Rossi R Poverini G Di Lullo A Modesti A Modica ML Scarino (1996) ArticleTitleHeavy metal toxicity following apical and basolateral exposure in the human intestinal cell line caco-2 Toxicol In Vitro 10 27–36 Occurrence Handle1:CAS:528:DyaK28XhsVylt78%3D Occurrence Handle10.1016/0887-2333(95)00097-6 Occurrence Handle20650179

    Article  CAS  PubMed  Google Scholar 

  • MJ Sahran H Roels R Lauwerys H Reyners E Gianfelicide Reyners (1986) ArticleTitleInfluence of manganese on the gastrointestinal absorption of cadmium in rats J Appl Toxicol 6 313–316

    Google Scholar 

  • JA Staessen HA Roels D Emelianov T Kuznetsova L Thijs J Vangronsveld R Fagard (1999) ArticleTitleEnvironmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group Lancet 353 1140–1144 Occurrence Handle10209978 Occurrence Handle1:STN:280:DyaK1M3isVKrtg%3D%3D Occurrence Handle10.1016/S0140-6736(98)09356-8

    Article  PubMed  CAS  Google Scholar 

  • J Tallkvist CL Bowlus B Lonnerdal (2001) ArticleTitleDMT1 gene expression and cadmium absorption in human absorptive enterocytes Toxicol Lett 122 171–177 Occurrence Handle11439223 Occurrence Handle1:CAS:528:DC%2BD3MXkvVenurY%3D Occurrence Handle10.1016/S0378-4274(01)00363-0

    Article  PubMed  CAS  Google Scholar 

  • DM Templeton (1990) ArticleTitleCadmium uptake by cells of renal origin J Biol Chem 265 21764–21770 Occurrence Handle2254329 Occurrence Handle1:CAS:528:DyaK3cXmtVKns78%3D

    PubMed  CAS  Google Scholar 

  • M Torra J To-Figueras M Rodamilans M Brunet J Corbella (1995) ArticleTitleCadmium and zinc relationships in the liver and kidney of humans exposed to environmental cadmium Sci Total Environ 170 53–57 Occurrence Handle7569880 Occurrence Handle1:CAS:528:DyaK2MXns1Gltr8%3D Occurrence Handle10.1016/0048-9697(95)04534-8

    Article  PubMed  CAS  Google Scholar 

  • T Watanabe O Iwami H Nakatsuka H Iguchi M Ikeda (1991) ArticleTitleCorrelation of cadmium, copper, manganese, and zinc levels in the urine of people in nonpolluted areas J Toxicol Environ Health 33 263–272 Occurrence Handle1856876 Occurrence Handle1:CAS:528:DyaK3MXlslKrtbY%3D Occurrence Handle10.1080/15287399109531525

    Article  PubMed  CAS  Google Scholar 

  • RT White P Kettisch P Kainrath (1998) ArticleTitleThe high pressure asher: a high-performance sample decomposition system as an alternative to microwave-assisted digestion Atomic Spectroscopy 19 187–192 Occurrence Handle1:CAS:528:DyaK1MXhslantro%3D

    CAS  Google Scholar 

  • T Yanagiya N Imura S Enomoto Y Kondo S Himeno (2000) ArticleTitleSuppression of a high-affinity transport system for manganese in cadmium-resistant metallothionein-null cells J Pharmacol Exp Therap 292 1080–1086 Occurrence Handle1:CAS:528:DC%2BD3cXhslWku78%3D

    CAS  Google Scholar 

  • A Zweibaum I Chantret (1989) Human colon carcinera cell lines as in vitro models for the study of cell differenciation MW Smith FV Sepulveda (Eds) Adaptation and Development of Gastrointestinal Function Manchester University Press Manchester, UK 103–112

    Google Scholar 

  • A Zweibaum M Laburthe E Grasset D Louvard (1991) Use of cultured cell lines in studies of intestinal cell differentiation and function MFaRA Frizzel (Eds) Handbook of Physiology: The Gastrointestinal System Am. Physiol. Soc Bethesda 223–255

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Unité Contaminants Inorganiques et Minéraux de l’Environnement (CIME) – Equipe Métaux Lourds et Eléments minéraux (MET), AFSSA LERQAP: 23, avenue du Général De Gaulle, F-94706, Maisons-Alfort cedex, France

    Laurent Noël, Thierry Guérin & Jean-Marc Frémy

  2. Laboratoire de Pharmacie-Toxicologie – Ecole Nationale Vétérinaire d’Alfort, 7, avenue du Général de Gaulle, 94704, Maisons-Alfort cedex, France

    Céline Huynh-Delerme & Hélène Huet

  3. Ecole Nationale Vétérinaire de Toulouse, 23, chemin des Capelles, 31076, Toulouse Cedex 03, France

    Martine Kolf-Clauw

Authors
  1. Laurent Noël
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Céline Huynh-Delerme
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thierry Guérin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hélène Huet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Marc Frémy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martine Kolf-Clauw
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laurent Noël.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Noël, L., Huynh-Delerme, C., Guérin, T. et al. Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a long-term Caco-2 TC7 cell model. Biometals 19, 473–481 (2006). https://doi.org/10.1007/s10534-005-5147-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-005-5147-y

Keywords

Search

Navigation