Pesticide toxicogenomics across scales: In vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

Immacolata Porreca, Fulvio D'Angelo, Lucia De Franceschi, Alessandro Mattè, Michele Ceccarelli, Achille Iolascon, Alberto Zamò, Filomena Russo, Maria Ravo, Roberta Tarallo, Marzia Scarfò, Alessandro Weisz, Mario De Felice, Massimo Mallardo, Concetta Ambrosino

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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.

Original languageEnglish
Article number38131
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 1 Dec 2016
Externally publishedYes

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Porreca, I., D'Angelo, F., De Franceschi, L., Mattè, A., Ceccarelli, M., Iolascon, A., Zamò, A., Russo, F., Ravo, M., Tarallo, R., Scarfò, M., Weisz, A., De Felice, M., Mallardo, M., & Ambrosino, C. (2016). Pesticide toxicogenomics across scales: In vitro transcriptome predicts mechanisms and outcomes of exposure in vivo. Scientific Reports, 6, [38131]. https://doi.org/10.1038/srep38131