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Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution.

BMC genomics (2014-12-06)
Immacolata Porreca, Fulvio D'Angelo, Daniela Gentilcore, Emanuele Carchia, Angela Amoresano, Andrea Affuso, Michele Ceccarelli, Pasquale De Luca, Libera Esposito, Francesco M Guadagno, Massimo Mallardo, Antonio Nardone, Sergio Maccarone, Francesca Pane, Marzia Scarfò, Paolo Sordino, Mario De Felice, Concetta Ambrosino
ABSTRACT

Comparison of toxicogenomic data facilitates the identification of deregulated gene patterns and maximizes health risk prediction in human. Here, we performed phenotypic anchoring on the effects of acute exposure to low-grade polluted groundwater using mouse and zebrafish. Also, we evaluated two windows of chronic exposure in mouse, starting in utero and at the end of lactation. Bioinformatic analysis of livers microarray data showed that the number of deregulated biofunctions and pathways is higher after acute exposure, compared to the chronic one. It also revealed specific profiles of altered gene expression in all treatments, pointing to stress response/mitochondrial pathways as major players of environmental toxicity. Of note, dysfunction of steroid hormones was also predicted by bioinformatic analysis and verified in both models by traditional approaches, serum estrogens measurement and vitellogenin mRNA determination in mice and zebrafish, respectively. In our report, phenotypic anchoring in two vertebrate model organisms highlights the toxicity of low-grade pollution, with varying susceptibility based on exposure window. The overlay of zebrafish and mice deregulated pathways, more than single genes, is useful in risk identification from chemicals implicated in the observed effects.

MATERIALS
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