Comparison of the sensitivity of different toxicological endpoints in Caco-2 cells after cadmium chloride treatment

Boveri, Monica; Pazos, Patricia; Gennari, Alessandra; Casado, Juan; Hartung, Thomas; Prieto, Pilar

doi:10.1007/s00204-003-0532-1

Cited by 26 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In various cell models, it has been previously shown that low doses of Cd markedly increased the expression of MT1X, HMOX-1 and HSP70 [12,[39][40][41][42][43][44][45][46][47] suggesting their usefulness as biomarkers for evaluating the toxicity of Cd at low doses and the ability of the cells to respond to such stress [15]. Our results showed that apical treatment strongly induced MT1X at non cytotoxic concentrations, with only a slight induction of HMOX-1 and no effect on HSP70 expression.…”

Section: Discussionsupporting

confidence: 47%

Characterisation of Cadmium Chloride Induced Molecular and Functional Alterations in Airway Epithelial Cells

Forti

Bulgheroni

Çetin

et al. 2010

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Epidemiological studies show that cadmium (Cd) exposure causes pulmonary damage, such as emphysema, pneumonitis, and lung cancer. However, the mechanisms leading to pulmonary toxicity are not yet fully elucidated. The aim of this study was to further investigate cadmium chloride (CdCl₂) induced toxicity using Calu-3 cells as an in vitro model of human bronchial epithelial cells. CdCl₂ induced effects following either apical or basolateral exposure were evaluated by Neutral Red Uptake (NRU), Trans-Epithelial Electrical Resistance (TEER), and alteration in Metallothionein 1X (MT1X), Heat shock protein 70 (HSP70), and Heme oxygenase 1 (HMOX-1) genes. CdCl₂ exposure resulted in a collapse of barrier function and the induction of MT1X, HMOX-1 and HSP70 genes, prior to alterations in cell viability. These effects were more pronounced when the exposure was from the basolateral side. Co-administration of N-Acetylcysteine (NAC) exerted a strong protective effect against CdCl₂ induced barrier damage and stress related genes, while other antioxidants only attenuated CdCl₂ induced HSP70 and HMOX-1 and showed no protective effect on the barrier collapse. These findings indicate that CdCl₂ exposure is likely to impair Calu-3 barrier function at non cytotoxic concentrations by a direct effect on adherens junction proteins. The protective effect of NAC against CdCl₂ induced MT1X, HSP70 and HMOX-1 genes, demonstrates an anti-oxidant effect of NAC in addition to Cd chelation.

show abstract

Section: Discussionsupporting

confidence: 47%

Characterisation of Cadmium Chloride Induced Molecular and Functional Alterations in Airway Epithelial Cells

Forti

Bulgheroni

Çetin

et al. 2010

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, we used long-term testing up to 10 lmol/l cadmium, a concentration previously shown not to be cytotoxic (Boveri et al 2004;Huynh-Delerme et al 2005). Some authors have studied the influence of a serum-free medium or a serum-supplemented medium (Finley et al 1995;Reeves et al 2001;Ranaldi et al 2003) on the cells.…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2006

View full text Add to dashboard Cite

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 micromol 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 micromol/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 micromol Cd/l exposure, and no variation was observed with copper.

show abstract

“…Although the culture media differ, all these studies have been performed using serum-free media. To our knowledge, there is no LC 50 value published for Cd in Caco-2 cells, but from FACScan analyses with PI, an LC 50 of about 75 lM can be estimated at 24 h (Boveri et al 2004). Also a 13-fold increase in LDH leakage was measured by Blais et al (1999) following a 24-h exposure to 24 lM Cd.…”

Section: Constitutive and Acquired Resistance To CD Vary With The Difmentioning

confidence: 99%

“…Damage to intestinal epithelium integrity, including increased paracellular permeability, altered cell viability and inflammatory response, have been reported following exposure to Cd (Duizer et al 1999;Boveri et al 2004;Berzina et al 2007). Cd also favors the production of oxygen species leading to oxidative stress (Wang et al 2004), and induces stress proteins such as MT-IIa, a metal-binding protein, and the heat shock protein HSP70 (Reeves and Rossow 1996;Kiang and Tsokos 1998;Blais et al 1999).…”

Section: Introductionmentioning

confidence: 97%

Resistance to cadmium as a function of Caco-2 cell differentiation: role of reactive oxygen species in cadmium- but not zinc-induced adaptation mechanisms

2009

View full text Add to dashboard Cite

Cadmium (Cd) is a highly toxic metal that enters the food chain. Following oral ingestion, the intestinal epithelium is the first biological barrier crossed by Cd and is also an important target tissue. In the present study, the human intestinal Caco-2 cell line was used to evaluate the impact of a low level of exposure on both undifferentiated and differentiated intestinal cells. As revealed by the LC(50) values estimated with the 3-[4,5-dimethyl-2-thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, mature Caco-2 cells were more resistant to Cd. However, following a 24-h exposure to non-cytotoxic levels of Cd (10 microM) or zinc (Zn, 100 microM), threefold increases were obtained in the LC(50) values of 7-day-old cells, whereas increased resistance in 21-day-old cells was observed exclusively with Zn. Induction of MT-IIa and HSP70 mRNAs was higher in undifferentiated cells and an increase in cellular glutathione (GSH) content was observed exclusively in these cell cultures. However, the results obtained with cycloheximide used for inhibiting protein synthesis and with L-buthionine sulfoximine (BSO), which inhibits GSH synthesis, revealed that protein synthesis is not a prerequisite to the development of resistance. The presence of 100 mM 3-amino-1,2,4-triazole (3AT), a catalase inhibitor, prevented Cd-induced but not Zn-induced resistance, as well as sensitized cells to Cd toxicity. These results show for the first time differences in constitutive and acquired resistance to Cd as a function of enterocytic differentiation status and suggest the involvement of different mechanisms for Cd- and Zn-induced adaptation in the intestinal cells. Redox signals may trigger Cd-induced adaptation mechanisms but pro-oxidant conditions would eliminate proliferative intestinal cells capability to develop resistance. This would be critical for Cd- but not Zn-induced mechanisms of resistance since Cd but not Zn may cause oxidative stress.

show abstract

Comparison of the sensitivity of different toxicological endpoints in Caco-2 cells after cadmium chloride treatment

Cited by 26 publications

References 27 publications

Characterisation of Cadmium Chloride Induced Molecular and Functional Alterations in Airway Epithelial Cells

Characterisation of Cadmium Chloride Induced Molecular and Functional Alterations in Airway Epithelial Cells

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

Resistance to cadmium as a function of Caco-2 cell differentiation: role of reactive oxygen species in cadmium- but not zinc-induced adaptation mechanisms

Contact Info

Product

Resources

About