Project description:Transcriptional profiling of mussel (Mytilus galloprovincialis) digestive gland tissue comparing control tissue with tissue obtained from animals exposed for four days to sublethal amounts of Nickel, Chlorpyrifos, or their mixture. Background: Mixtures of chemicals present in aquatic environments may elicit toxicity due to additive or synergistic effects among the constituents or ‘vice versa’ the adverse outcome may be reduced by antagonistic interactions. Deviations from additivity should be explained either by the perturbations of toxicokinetic parameters and/or chemical toxicodynamics. We addressed this important question in marine mussels exposed subchronically to a binary mixture made of two wide-spread pollutants: the heavy metal Nickel and the organic phosphorus pesticide Chlorpyrifos. To this aim, we proposed the use of a systems approach based on the evaluation and integration of different disciplines, i.e. high throughput gene expression profiling, functional genomics, stress biomakers and toxicokinetics. Results: Stress biomarkers showed statistically significant antagonistic deviations from the reference model systems to predict mixture toxicity which are based either on simple additivity or non-interaction. While toxicokinetic modeling did not explain mixture interactions, gene expression profiling and further functional genomics analysis provided clues that the decrement of toxicity may arise from the development of specific toxicodynamics. Multivariate statistics of microarray and quantitative PCR data showed two separate patterns for the single chemicals and a composite complex profile for the mixture suggesting the occurrence of interactive molecular responses. The latter signature accounted for differentially expressed genes whose relative expression values were either in trend or in contrast with those found due to single substance treatments and a relevant set of sequences which were exclusive of the mixture gene list. Conclusion: The functional genomics assessment fits with biological data to indicate the occurrence of different toxicodynamic events and ‘in general’ a decrease of toxicity, driven by the mitigation or even abolishment of lysosomal responses such as the lipid metabolic disorder observed exclusively in single chemical-exposed samples. Furthermore, our results emphasized the importance of the application of mechanistic approaches and the power of systems assessment to study toxicological responses in ecological relevant organisms.

Project description:Transcriptional profiling of mussel (Mytilus galloprovincialis) digestive gland tissue comparing control tissue with tissue obtained from animals exposed for four days to sublethal amounts of Nickel, Chlorpyrifos, or their mixture. Background: Mixtures of chemicals present in aquatic environments may elicit toxicity due to additive or synergistic effects among the constituents or ‘vice versa’ the adverse outcome may be reduced by antagonistic interactions. Deviations from additivity should be explained either by the perturbations of toxicokinetic parameters and/or chemical toxicodynamics. We addressed this important question in marine mussels exposed subchronically to a binary mixture made of two wide-spread pollutants: the heavy metal Nickel and the organic phosphorus pesticide Chlorpyrifos. To this aim, we proposed the use of a systems approach based on the evaluation and integration of different disciplines, i.e. high throughput gene expression profiling, functional genomics, stress biomakers and toxicokinetics. Results: Stress biomarkers showed statistically significant antagonistic deviations from the reference model systems to predict mixture toxicity which are based either on simple additivity or non-interaction. While toxicokinetic modeling did not explain mixture interactions, gene expression profiling and further functional genomics analysis provided clues that the decrement of toxicity may arise from the development of specific toxicodynamics. Multivariate statistics of microarray and quantitative PCR data showed two separate patterns for the single chemicals and a composite complex profile for the mixture suggesting the occurrence of interactive molecular responses. The latter signature accounted for differentially expressed genes whose relative expression values were either in trend or in contrast with those found due to single substance treatments and a relevant set of sequences which were exclusive of the mixture gene list. Conclusion: The functional genomics assessment fits with biological data to indicate the occurrence of different toxicodynamic events and ‘in general’ a decrease of toxicity, driven by the mitigation or even abolishment of lysosomal responses such as the lipid metabolic disorder observed exclusively in single chemical-exposed samples. Furthermore, our results emphasized the importance of the application of mechanistic approaches and the power of systems assessment to study toxicological responses in ecological relevant organisms. Mussel MytArray 1.0 (Platform GPL1799)-based arrays: Three-condition experiment. Dual color competitive hybridizations. Common reference (vehicle treated animals, 0.02% Dimethyl sulfoxide); Pools of six animals. Biological replicates: 4 controls, 4 Nickel, 4 Chlorpyrifos. One replicate per array. Mussel MytArray 1.1 (Platform GPL10269)-based arrays: Four-condition experiment. Dual color competitive hybridizations. Common reference (vehicle treated animals, 0.02% Dimethyl sulfoxide); Pools of six animals. Biological replicates: 5 controls, 1 Nickel, 3 Chlorpyrifos, 5 mixture. One replicate per array.

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Mytilus galloprovincialis

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