In vitro and bioinformatics mechanistic-based approach for cadmium carcinogenicity understanding.

Animals Cadmium / toxicity Carcinogenesis / chemically induced Carcinogens / toxicity Cell Line Cell Transformation, Neoplastic / genetics Computational Biology Cytokines / genetics Gene Expression Regulation, Neoplastic / drug effects Mice
Cadmium Carcinogenesis Cell transformation assay Toxicogenomics

Journal

Toxicology in vitro : an international journal published in association with BIBRA
ISSN: 1879-3177
Titre abrégé: Toxicol In Vitro
Pays: England
ID NLM: 8712158

Informations de publication

Date de publication:
Jun 2020
Historique:
received: 18 09 2019
revised: 28 11 2019
accepted: 01 01 2020
pubmed: 7 1 2020
medline: 30 1 2021
entrez: 7 1 2020
Statut: ppublish

Résumé

Cadmium is a toxic metal able to enter the cells through channels and transport pathways dedicated to essential ions, leading, among others, to the dysregulation of divalent ions homeostasis. Despite its recognized human carcinogenicity, the mechanisms are still under investigation. A powerful tool for mechanistic studies of carcinogenesis is the Cell Transformation Assay (CTA). We have isolated and characterized by whole genome microarray and bioinformatics analysis of differentially expressed genes (DEGs) cadmium-transformed cells from different foci (F1, F2, and F3) at the end of CTA (6 weeks). The systematic analysis of up- and down-regulated transcripts and the comparison of DEGs in transformed cells evidence different functional targets and the complex picture of cadmium-induced transformation. Only 34 in common DEGs are found in cells from all foci, and among these, only 4 genes are jointly up-regulated (Ccl2, Ccl5, IL6 and Spp1), all responsible for cytokines/chemokines coding. Most in common DEGs are down-regulated, suggesting that the switching-off of specific functions plays a major role in this process. In addition, the comparison of dysregulated pathways immediately after cadmium treatment with those in transformed cells provides a valuable means to the comprehension of the overall process.

Identifiants

DOI: 10.1016/j.tiv.2020.104757 PMID: 31904401 PMC: PMC7166080
pubmed: 31904401
pii: S0887-2333(19)30719-2
doi: 10.1016/j.tiv.2020.104757
pmc: PMC7166080
pii:
doi:

Substances chimiques

Carcinogens 0
Cytokines 0
Cadmium 00BH33GNGH

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104757

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Monica Oldani (M)

Department of Biotechnology and Biosciences, University of Milan - Bicocca, Piazza della Scienza 3, 20126 Milan, Italy.

Marco Fabbri (M)

Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA.

Pasquale Melchioretto (P)

Department of Earth and Environmental Sciences, University of Milan - Bicocca, Piazza della Scienza 1, 20126 Milan, Italy.

Giulia Callegaro (G)

Department of Earth and Environmental Sciences, University of Milan - Bicocca, Piazza della Scienza 1, 20126 Milan, Italy; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, The Netherlands.

Paola Fusi (P)

Department of Biotechnology and Biosciences, University of Milan - Bicocca, Piazza della Scienza 3, 20126 Milan, Italy; Integrated Models for Prevention and Protection in Environmental and Occupational Health, (MISTRAL) Interuniversity Research Center, Italy.

Laura Gribaldo (L)

European Commission, DG Joint Research Centre, Via Fermi 2749, 21027 Ispra, VA, Italy. Electronic address: laura.gribaldo@ec.europa.eu.

Matilde Forcella (M)

Department of Biotechnology and Biosciences, University of Milan - Bicocca, Piazza della Scienza 3, 20126 Milan, Italy.

Chiara Urani (C)

Department of Earth and Environmental Sciences, University of Milan - Bicocca, Piazza della Scienza 1, 20126 Milan, Italy; Integrated Models for Prevention and Protection in Environmental and Occupational Health, (MISTRAL) Interuniversity Research Center, Italy.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux lourds › Cadmium › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › Actions chimiques et utilisations › Actions toxiques › Noxas › Cancérogènes › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Transformation cellulaire néoplasique › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › Sciences de l'information › Informatique › Biologie informatique › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › In vitro and bioinformatics mechanistic-based...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › In vitro and bioinformatics mechanistic-based...