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Cadmium-induced differential toxicogenomic response in resistant and sensitive mouse strains undergoing neurulation.

ABSTRACT: Common inbred mouse strains, such as the C57BL/6 (C57) and the SWV, display differences in sensitivity to environmental teratogens during gestation. For example, the C57 is more sensitive than the SWV to cadmium (Cd) exposure during neurulation, inducing a higher incidence of neural tube defects (NTDs). Here, we report, using Cd as a model teratogen, the first large scale toxicogenomic study to compare teratogen-induced gene expression alterations in C57 and SWV embryos undergoing neurulation, identifying toxicogenomic responses that associate with developmental toxicity and differential sensitivity. Using a systems-based toxicogenomic approach, comparing Cd-exposed and control C57 and SWV embryos (12- and 24-h postinjection [p.i.] [gestational day 8.0, ip]), we examined differentially expressed genes at multiple levels (biological process, pathway, gene) using Gene Ontology (GO) analysis, pathway mapping and cross-scatter plots. In both C57 and SWV embryos, we observed several gene expression alterations linked with cell cycle-related classifications, however, only in the C57 we observed upregulation of p53-dependent mediators Ccng1 and Pmaip1, previously associated with cell cycle arrest, apoptosis and NTD formation. In addition, we also identified a greater reduction in expression of nervous system development-related genes (e.g., Zic1, En2, Neurog1, Elavl4, Metrn, Nr2f1, Nr2f2) in the C57 compared to the SWV (12-h p.i.). In summary, our results indicate that differences in Cd-induced gene expression profiles between NTD resistant and sensitive strains within enriched biological processes (including developmental and cell cycle-related categories) associate with increased sensitivity to developmental toxicity as determined by observations of increased NTD formation, mortality (resorptions) and reduced fetal growth. Such observations may provide more detailed and useful mechanistic clues for identification of differences in life-stage specific teratogenic response.

SUBMITTER: Robinson JF

PROVIDER: S-EPMC2768398 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Cadmium-induced differential toxicogenomic response in resistant and sensitive mouse strains undergoing neurulation.

Robinson Joshua F JF Yu Xiaozhong X Hong Sungwoo S Griffith William C WC Beyer Richard R Kim Euvin E Faustman Elaine M EM

Toxicological sciences : an official journal of the Society of Toxicology 20081029 1

Common inbred mouse strains, such as the C57BL/6 (C57) and the SWV, display differences in sensitivity to environmental teratogens during gestation. For example, the C57 is more sensitive than the SWV to cadmium (Cd) exposure during neurulation, inducing a higher incidence of neural tube defects (NTDs). Here, we report, using Cd as a model teratogen, the first large scale toxicogenomic study to compare teratogen-induced gene expression alterations in C57 and SWV embryos undergoing neurulation, i ...[more]

PMID: 18974090

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Project description:The goal of this study was to identify Cd-resistant bacterial strains with endurance capacity and to evaluate their ability to remove cadmium ions from cadmium-polluted water. The Bacillus cereusS5 strain identified in this study had the closest genetic relationship with B. cereus sp. Cp1 and performed well in the removal of Cd2+ions from solution. The results showed that both the live and dead biomasses of the Cd2+-tolerant B. cereus S5 strain could absorb Cd2+ ions in solution but that the live biomass of the B. cereus S5 strain outperformed the dead biomass at lower Cd2+concentrations. An analysis of the cadmium tolerance genes of B. cereus S5 identified ATPase genes that were associated with cadmium tolerance and involved in the ATP pumping mechanism. The FTIR spectra revealed the presence of amino, carboxyl and hydroxyl groups on the pristine biomass and indicated that the cadmium ion removal ability was related to the structure of the strain. The maximum absorption capacity of the B. cereus S5 strain in viable spore biomass was 70.16 mg/g (dry weight) based on a pseudo-second-order kinetic model fit to the experimental data. The Langmuir and Langmuir-Freundlich isotherm adsorption models fit the cadmium ion adsorption data well, and the kinetic curves indicated that the adsorption rate was second-order. For Cd2+ concentrations (mg/L) of 1-109 mg/L, good removal efficiency (>80%) was achieved using approximately 3.48-10.3 g/L of active spore biomass of the B. cereus S5 strain. A cadmium-tolerant bacteria-activated carbon-immobilized column could be used for a longer duration and exhibited greater treatment efficacy than the control column in the treatment of cadmium-polluted water. In addition, a toxicity assessment using mice demonstrated that the biomass of the B. cereus S5 strain and its fermentation products were non-toxic. Thus, the isolated B. cereus S5 strain can be considered an alternative biological adsorbent for use in emergency responses to severe cadmium pollution and in the routine treatment of trace cadmium pollution.

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Cadmium-induced differential toxicogenomic response in resistant and sensitive mouse strains undergoing neurulation.

Publications

Cadmium-induced differential toxicogenomic response in resistant and sensitive mouse strains undergoing neurulation.

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