title: Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo.
abstract: In vitro Omics analysis (i.e. transcriptome) is suggested to predict in vivo toxicity and adverse effects in humans, although the causal link between high-throughput data and effects in vivo is not easily established. Indeed, the chemical-organism interaction can involve processes, such as adaptation, not established in cell cultures. Starting from this consideration we investigate the transcriptomic response of immortalized thyrocytes to ethylenthiourea and chlorpyrifos. In vitro data revealed specific and common genes/mechanisms of toxicity, controlling the proliferation/survival of the thyrocytes and unrelated hematopoietic cell lineages. These results were phenotypically confirmed in vivo by the reduction of circulating T4 hormone and the development of pancytopenia after long exposure. Our data imply that in vitro toxicogenomics is a powerful tool in predicting adverse effects in vivo, experimentally confirming the vision described as Tox21c (Toxicity Testing in the 21st century) although not fully recapitulating the biocomplexity of a living animal.
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Porreca
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: D'Angelo
authors.affiliation: Department of Medicine, University of Verona-AOUI Verona, Policlinico GB Rossi, P.Le L. Scuro, 10, 37134 Verona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: De Franceschi
authors.affiliation: Department of Medicine, University of Verona-AOUI Verona, Policlinico GB Rossi, P.Le L. Scuro, 10, 37134 Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mattè
authors.affiliation: Department of Science and Technology, University of Sannio, Via Port'Arsa 11, 82100, Benevento, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ceccarelli
authors.affiliation: Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II Napoli, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
authors.affiliation: Department of Diagnostics and Public Health, University of Verona-AOUI Verona, Policlinico GB Rossi, P.Le L. Scuro, 10, 37134 Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zamò
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Russo
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Schola Medica Salernitana', University of Salerno, Baronissi, Salerno, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ravo
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Schola Medica Salernitana', University of Salerno, Baronissi, Salerno, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Tarallo
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Scarfò
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Schola Medica Salernitana', University of Salerno, Baronissi, Salerno, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
authors.affiliation: IEOS-CNR, Via Pansini 6, 80131 Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: De Felice
authors.affiliation: Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II Napoli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mallardo
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.|Department of Science and Technology, University of Sannio, Via Port'Arsa 11, 82100, Benevento, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Ambrosino
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000633:toxicity; D005031:Ethylenethiourea / Q000633:toxicity; D005260:Female; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D010575:Pesticides; D005031:Ethylenethiourea; D004390:Chlorpyrifos