Please use this identifier to cite or link to this item:
|Title:||Toxicogenomics applied to in vitro Cell Transformation Assay reveals mechanisms of early response to cadmium|
|Authors:||CALLEGARO G.; FORCELLA MATILDE; MELCHIORETTO PASQUALE; FRATTINI ANNALISA; GRIBALDO LAURA; FUSI PAOLA; FABBRI MARCO; URANI CHIARA|
|Citation:||TOXICOLOGY IN VITRO vol. 48 p. 232-243|
|Publisher:||PERGAMON-ELSEVIER SCIENCE LTD|
|Type:||Articles in periodicals and books|
|Abstract:||Cadmium is a well recognized carcinogen, primarily released into the environment by anthropogenic activities. In the effort to understand the early events responsible for cadmium carcinogenesis, we have used an in vitro biological system (the Cell Transformation Assay, CTA), that has been shown to closely model some key stages of the conversion of normal cells into malignant ones. Cadmium-triggered early responses in CTA were analysed through microarray-based toxicogenomics. Metallothioneins represent the earliest cell response, together with Slc30a1 encoding for a ZnT-1 zinc exporter. Other genes were found to be up-regulated in the first 24 hours following Cd administration: phospatidylinositol-4-phospate 5-kinase alpha (Pip5k1a), glutathione S-transferase (Gsta 1-3), Gdf15 and aldolase. However, after the exposure, a number of genes expressing zinc proteins were found to be down-regulated, amongst which were many olfactory receptors (ORs) coding genes. Cd administration also promoted massive Zn release inside the cell that could be related to moonlighting activities of regulated genes (proteins). On the whole our data suggest that, despite the early involvement of defence mechanisms (metallothionein and GST), the Zn release triggered by Cd, as well as Cd interference with different proteins, may lead to gene expression alterations which later induce metabolic changes and direct the cells towards uncontrolled growth.|
|JRC Directorate:||Health, Consumers and Reference Materials|
Files in This Item:
There are no files associated with this item.
Items in repository are protected by copyright, with all rights reserved, unless otherwise indicated.