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Application of physiologically based modelling and transcriptomics to probe the systems toxicology of aldicarb for Caenorhabditis elegans (Maupas 1900)

Identifieur interne : 001959 ( Istex/Curation ); précédent : 001958; suivant : 001960

Application of physiologically based modelling and transcriptomics to probe the systems toxicology of aldicarb for Caenorhabditis elegans (Maupas 1900)

Auteurs : Jodie F. Wren [Royaume-Uni] ; Peter Kille [Royaume-Uni] ; David J. Spurgeon [Royaume-Uni] ; Suresh Swain [Royaume-Uni] ; Stephen R. Sturzenbaum [Royaume-Uni] ; Tjalling Jager [Pays-Bas]

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RBID : ISTEX:3D5F45D60B940D2FAE5038B76D41CCD4788C70A4

English descriptors

Abstract

Abstract: The toxicity of aldicarb on movement, life cycle, population growth rate and resource allocation, and the gene expression changes underpinning these effects, were investigated for Caenorhabditis elegans. A clear effect of aldicarb on nematode movement was found suggesting that this pesticide acts as a neurotoxicant. Aldicarb also had an effect on life cycle traits including low concentration life-span extension; high concentration brood size reduction and a high concentration extension of time to first egg. All life-cycle and growth data were integrated into a biology-based model (DEBtox) to characterise aldicarb effects on life-history traits, resource allocation and population growth rate within a single modelling framework. The DEBtox fits described concentration dependent effects on individual traits and population growth rate and indicated that the most probable mechanism of action of the pesticide was an increase in energy demands for somatic and reproductive tissue maintenance. Transcriptomic profiling indicated that aldicarb was associated with changes in amino acid metabolism, DNA structure, fatty acid metabolism and cytochrome P450 mediated xenobiotic metabolism. The changes in the amino acid and fatty acid pathways suggest an effect of aldicarb on protein integrity; while effects on DNA suggests that aldicarb influence DNA morphology or replication. Both these effects have the potential to incur increased costs for structural maintenance of macromolecules. These effects, coupled to the effect on biotransformation enzymes also seen, represent the materialisation of the maintenance costs indicated by DEBtox modelling.

Url:
DOI: 10.1007/s10646-010-0591-z

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ISTEX:3D5F45D60B940D2FAE5038B76D41CCD4788C70A4

Le document en format XML

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<div type="abstract" xml:lang="en">Abstract: The toxicity of aldicarb on movement, life cycle, population growth rate and resource allocation, and the gene expression changes underpinning these effects, were investigated for Caenorhabditis elegans. A clear effect of aldicarb on nematode movement was found suggesting that this pesticide acts as a neurotoxicant. Aldicarb also had an effect on life cycle traits including low concentration life-span extension; high concentration brood size reduction and a high concentration extension of time to first egg. All life-cycle and growth data were integrated into a biology-based model (DEBtox) to characterise aldicarb effects on life-history traits, resource allocation and population growth rate within a single modelling framework. The DEBtox fits described concentration dependent effects on individual traits and population growth rate and indicated that the most probable mechanism of action of the pesticide was an increase in energy demands for somatic and reproductive tissue maintenance. Transcriptomic profiling indicated that aldicarb was associated with changes in amino acid metabolism, DNA structure, fatty acid metabolism and cytochrome P450 mediated xenobiotic metabolism. The changes in the amino acid and fatty acid pathways suggest an effect of aldicarb on protein integrity; while effects on DNA suggests that aldicarb influence DNA morphology or replication. Both these effects have the potential to incur increased costs for structural maintenance of macromolecules. These effects, coupled to the effect on biotransformation enzymes also seen, represent the materialisation of the maintenance costs indicated by DEBtox modelling.</div>
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