Cytotoxicity and induction of protective mechanisms in HepG2 cells exposed to cadmium.
Cadmium is a widespread industrial pollutant. The primary route of exposure occurs via contaminated drinking water or food supplies, and tobacco. Its chronic introduction and ingestion lead to bio-magnification in target organs, as the liver. The aim of this paper is to determine Cd cytotoxic concentrations in the human hepatoma cell line HepG2. Further aims are the study of the activation and involvement of protection mechanisms against Cd hepatotoxicity. Cd was accumulated within the cells, as measured by ICP-AES. Metallothioneins (MT-1 and -2), a family of metal-binding proteins, were induced in a dose-dependent way after treatment with concentrations below the IC(50) value (mean value 22 microM). The over-expression of MT by Zn pre-treatment was able to defend against Cd cytotoxicity. Heat shock protein 70 kDa (hsp70) was induced at high non-cytotoxic concentrations (5, 10 microM) probably as a consequence of proteotoxicity, but its over-expression by a sub-lethal heat shock was not able to protect the cells from Cd cytotoxic concentrations (20, 50, 100 microM).
Urani
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Dipartimento di Scienze dell'Ambiente e del Territorio, Università degli Studi di Milano Bicocca, piazza della Scienza, 1 20126 Milano, Italy. chiara.urani@unimib.it
Melchioretto
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Canevali
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Crosta
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GF
D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008668:Metallothionein / Q000096:biosynthesis / Q000378:metabolism; D015854:Up-Regulation; D015032:Zinc / Q000494:pharmacology
D018840:HSP70 Heat-Shock Proteins; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc