Interactions of a pesticide/heavy metal mixture in marine bivalves: a transcriptomic assessment
Identifieur interne : 000030 ( Pmc/Curation ); précédent : 000029; suivant : 000031Interactions of a pesticide/heavy metal mixture in marine bivalves: a transcriptomic assessment
Auteurs : Francesco Dondero [Italie] ; Mohamed Banni [Italie, Tunisie] ; Alessandro Negri [Italie] ; Lara Boatti [Italie] ; Alessandro Dagnino [Italie] ; Aldo Viarengo [Italie]Source :
- BMC Genomics [ 1471-2164 ] ; 2011.
Abstract
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 carried out in tissues of
Cellular and tissue biomarkers, viz. digestive gland lysosomal membrane stability, lysosomal/cytosol volume ratio, neutral lipid content and gill acetylcholinesterase activity were, in general, altered by either the exposure to nickel and Chlorpyrifos. However, their joint action rendered (i) an overall decrease of the stress syndrome level, as evaluated through an expert system integrating biomarkers and (ii) statistically significant antagonistic deviations from the reference model systems to predict mixture toxicity. While toxicokinetic modeling did not explain mixture interactions, gene expression profiling and further Gene Ontology-based functional genomics analysis provided clues that the decrement of toxicity may arise from the development of specific toxicodynamics. Multivariate statistics of microarray data (238 genes in total, representing about 14% of the whole microarray catalogue) showed two separate patterns for the single chemicals: the one belonging to the heavy metal -135 differentially expressed genes (DEGs) was characterized by the modulation of transcript levels involved in nucleic acid metabolism, cell proliferation and lipid metabolic processes. Chlorpyrifos exposure (43 DEGs) yielded a molecular signature which was biased towards carbohydrate catabolism (indeed, chitin metabolism) and developmental processes. The exposure to the mixture (103 DEGs) elicited a composite complex profile which encompassed the core properties of the pesticide but also a relevant set of unique features. Finally, the relative mRNA abundance of twelve genes was followed by Q-PCR to either confirm or complement microarray data. These results, in general, were compatible with those from arrays and indeed confirmed the association of the relative abundance of two GM-2 ganglioside activator genes in the development of the hyperlipidosis syndrome observed in digestive gland lysosomes of single chemical exposed mussels.
The transcriptomic assessment fitted with biological data to indicate the occurrence of different toxicodynamic events and, in general, a decrease of toxicity, driven by the mitigation or even abolition of lysosomal responses. Furthermore, our results emphasized the importance of the application of mechanistic approaches and the power of systems assessment to study toxicological responses in ecologically relevant organisms.
Url:
DOI: 10.1186/1471-2164-12-195
PubMed: 21496282
PubMed Central: 3094310
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>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 carried out in tissues of <italic>Mytius galloprovincialis </italic>
(Lam) 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.</p>
</sec>
<sec><title>Results</title>
<p>Cellular and tissue biomarkers, viz. digestive gland lysosomal membrane stability, lysosomal/cytosol volume ratio, neutral lipid content and gill acetylcholinesterase activity were, in general, altered by either the exposure to nickel and Chlorpyrifos. However, their joint action rendered (i) an overall decrease of the stress syndrome level, as evaluated through an expert system integrating biomarkers and (ii) statistically significant antagonistic deviations from the reference model systems to predict mixture toxicity. While toxicokinetic modeling did not explain mixture interactions, gene expression profiling and further Gene Ontology-based functional genomics analysis provided clues that the decrement of toxicity may arise from the development of specific toxicodynamics. Multivariate statistics of microarray data (238 genes in total, representing about 14% of the whole microarray catalogue) showed two separate patterns for the single chemicals: the one belonging to the heavy metal -135 differentially expressed genes (DEGs) was characterized by the modulation of transcript levels involved in nucleic acid metabolism, cell proliferation and lipid metabolic processes. Chlorpyrifos exposure (43 DEGs) yielded a molecular signature which was biased towards carbohydrate catabolism (indeed, chitin metabolism) and developmental processes. The exposure to the mixture (103 DEGs) elicited a composite complex profile which encompassed the core properties of the pesticide but also a relevant set of unique features. Finally, the relative mRNA abundance of twelve genes was followed by Q-PCR to either confirm or complement microarray data. These results, in general, were compatible with those from arrays and indeed confirmed the association of the relative abundance of two GM-2 ganglioside activator genes in the development of the hyperlipidosis syndrome observed in digestive gland lysosomes of single chemical exposed mussels.</p>
</sec>
<sec><title>Conclusion</title>
<p>The transcriptomic assessment fitted with biological data to indicate the occurrence of different toxicodynamic events and, in general, a decrease of toxicity, driven by the mitigation or even abolition of lysosomal responses. Furthermore, our results emphasized the importance of the application of mechanistic approaches and the power of systems assessment to study toxicological responses in ecologically relevant organisms.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Genomics</journal-id>
<journal-title-group><journal-title>BMC Genomics</journal-title>
</journal-title-group>
<issn pub-type="epub">1471-2164</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21496282</article-id>
<article-id pub-id-type="pmc">3094310</article-id>
<article-id pub-id-type="publisher-id">1471-2164-12-195</article-id>
<article-id pub-id-type="doi">10.1186/1471-2164-12-195</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Interactions of a pesticide/heavy metal mixture in marine bivalves: a transcriptomic assessment</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes" id="A1"><name><surname>Dondero</surname>
<given-names>Francesco</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>francesco.dondero@mfn.unipmn.it</email>
</contrib>
<contrib contrib-type="author" id="A2"><name><surname>Banni</surname>
<given-names>Mohamed</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<xref ref-type="aff" rid="I2">2</xref>
<email>m_banni@yahoo.fr</email>
</contrib>
<contrib contrib-type="author" id="A3"><name><surname>Negri</surname>
<given-names>Alessandro</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>alessandro.negri@mfn.unipmn.it</email>
</contrib>
<contrib contrib-type="author" id="A4"><name><surname>Boatti</surname>
<given-names>Lara</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>lara.boatti@mfn.unipmn.it</email>
</contrib>
<contrib contrib-type="author" id="A5"><name><surname>Dagnino</surname>
<given-names>Alessandro</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>alessandro.dagnino@mfn.unipmn.it</email>
</contrib>
<contrib contrib-type="author" id="A6"><name><surname>Viarengo</surname>
<given-names>Aldo</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>viarengo@mfn.unipmn.it</email>
</contrib>
</contrib-group>
<aff id="I1"><label>1</label>
Department of Environmental and Life Sciences, Università del Piemonte Orientale Amedeo Avogadro, 15121 Alessandria, Italy</aff>
<aff id="I2"><label>2</label>
Laboratory of Biochemistry and Environmental Toxicology, ISA, Chott-Mariem, 4042, Sousse, Tunisia</aff>
<pub-date pub-type="collection"><year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>16</day>
<month>4</month>
<year>2011</year>
</pub-date>
<volume>12</volume>
<fpage>195</fpage>
<lpage>195</lpage>
<history><date date-type="received"><day>27</day>
<month>4</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>16</day>
<month>4</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright ©2011 Dondero et al; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>Dondero et al; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://www.biomedcentral.com/1471-2164/12/195"></self-uri>
<abstract><sec><title>Background</title>
<p>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 carried out in tissues of <italic>Mytius galloprovincialis </italic>
(Lam) 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.</p>
</sec>
<sec><title>Results</title>
<p>Cellular and tissue biomarkers, viz. digestive gland lysosomal membrane stability, lysosomal/cytosol volume ratio, neutral lipid content and gill acetylcholinesterase activity were, in general, altered by either the exposure to nickel and Chlorpyrifos. However, their joint action rendered (i) an overall decrease of the stress syndrome level, as evaluated through an expert system integrating biomarkers and (ii) statistically significant antagonistic deviations from the reference model systems to predict mixture toxicity. While toxicokinetic modeling did not explain mixture interactions, gene expression profiling and further Gene Ontology-based functional genomics analysis provided clues that the decrement of toxicity may arise from the development of specific toxicodynamics. Multivariate statistics of microarray data (238 genes in total, representing about 14% of the whole microarray catalogue) showed two separate patterns for the single chemicals: the one belonging to the heavy metal -135 differentially expressed genes (DEGs) was characterized by the modulation of transcript levels involved in nucleic acid metabolism, cell proliferation and lipid metabolic processes. Chlorpyrifos exposure (43 DEGs) yielded a molecular signature which was biased towards carbohydrate catabolism (indeed, chitin metabolism) and developmental processes. The exposure to the mixture (103 DEGs) elicited a composite complex profile which encompassed the core properties of the pesticide but also a relevant set of unique features. Finally, the relative mRNA abundance of twelve genes was followed by Q-PCR to either confirm or complement microarray data. These results, in general, were compatible with those from arrays and indeed confirmed the association of the relative abundance of two GM-2 ganglioside activator genes in the development of the hyperlipidosis syndrome observed in digestive gland lysosomes of single chemical exposed mussels.</p>
</sec>
<sec><title>Conclusion</title>
<p>The transcriptomic assessment fitted with biological data to indicate the occurrence of different toxicodynamic events and, in general, a decrease of toxicity, driven by the mitigation or even abolition of lysosomal responses. Furthermore, our results emphasized the importance of the application of mechanistic approaches and the power of systems assessment to study toxicological responses in ecologically relevant organisms.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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