Carbendazim induced genomic instability in yeast
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE112062 | GEO | 2018/03/21
REPOSITORIES: GEO
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Project description:Pesticides are continuously released into the environment, with possible long-term consequences on aquatic organisms. One of the pesticides still applied in several crops in some countries is the fungicide carbendazim, ending up in surface waters with concentrations reaching 5 µg/L. Daphnia magna (clone k6) was used in this study as a model organism and it was exposed to a sub-lethal concentration of carbendazim (5 µg/L) for twelve generations. Gene expression alterations induced by this compound were assessed in the F0 and F12 generations using D. magna custom microarrays. Results revealed that carbendazim caused changes at the gene expression level in both generations. Genes involved in response to stress, DNA replication/repair, neurotransmission, protein biosynthesis, ATP production, lipids and carbohydrates metabolism were the most affected in both F0 and F12, although a lower number of differentially expressed genes were observed in the F12 generation exposed to carbendazim. The exposure of daphnids to carbendazim did not cause a stable change in gene expression from F0 to F12 generations. Effects at the gene expression level were early detected at the F0 generation after a short-time exposure (10 days), highlighting the advantages of using high throughput tools as early warning analysis but also providing information on chemical mode of action, which can add value in risk assessment procedures.
2017-05-01 | GSE78120 | GEO
Project description:Pesticides are continuously released into the environment, with possible long-term consequences on aquatic organisms. One of the pesticides still applied in several crops in some countries is the fungicide carbendazim, ending up in surface waters with concentrations reaching 5 µg/L. Daphnia magna (clone k6) was used in this study as a model organism and it was exposed to a sub-lethal concentration of carbendazim (5 µg/L) for twelve generations. Gene expression alterations induced by this compound were assessed in the F0 and F12 generations using D. magna custom microarrays. Results revealed that carbendazim caused changes at the gene expression level in both generations. Genes involved in response to stress, DNA replication/repair, neurotransmission, protein biosynthesis, ATP production, lipids and carbohydrates metabolism were the most affected in both F0 and F12, although a lower number of differentially expressed genes were observed in the F12 generation exposed to carbendazim. The exposure of daphnids to carbendazim did not cause a stable change in gene expression from F0 to F12 generations. Effects at the gene expression level were early detected at the F0 generation after a short-time exposure (10 days), highlighting the advantages of using high throughput tools as early warning analysis but also providing information on chemical mode of action, which can add value in risk assessment procedures. For the microarray experiment, neonates with less than 24h were picked from the F0 and F12 generations from both clean medium and carbendazim. Three replicates per each treatment were used and consisted of 5 daphnids aging 10 days old. A total of three replicates per treatment were used and each biological replicate was individually hybridized on the array. A single-color design was used, using the Agilent one-color RNA Spike-In Kit (AgilentTechnologies, Santa Clara, CA, USA), following the manufacturers protocol.
2017-05-01 | E-GEOD-78120 | biostudies-arrayexpress
Project description:Background: Molecular mechanisms of response to pesticides are scarce and information on such responses from soil invertebrates is almost inexistent. Enchytraeus albidus (Oligochaeta) is a standard soil ecotoxicology model species for which effects of many pesticides are known on survival, reproduction and avoidance behaviour. With the recent microarray development additional information can be retrieved on the molecular effects. Methodology/Principal Findings: Experiments were performed to investigate the transcription responses of E. albidus when exposed to three pesticides M-bM-^@M-^S dimethoate (insecticide), atrazine (herbicide) and carbendazim (fungicide) M-bM-^@M-^S in a range of concentrations that inhibited reproduction by 10%, 20%, 50% and 90% (EC10, EC20, EC50 and EC90, respectively). The goal of this study was to further identify key biological processes affected by each compound and if dose-related. All three pesticides significantly affected biological processes like translation, regulation of the cell cycle or general response to stress. Intracellular signalling and microtubule-based movement were affected by dimethoate and carbendazim whereas atrazine affected lipid and steroid metabolism (also by dimethoate) or carbohydrate metabolism (also by carbendazim). Response to DNA damage/DNA repair was exclusively affected by carbendazim. Conclusions: Changes in gene expression were significantly altered after 2 days of exposure in a dose-related manner. The mechanisms of response were comparable with the ones for mammals, suggesting across species conserved modes of action. The present results indicate the potential of using gene expression in risk assessment and the advantage as early markers. Gene expression in E.albidus was measured at 2 days after exposure to dimethoate, atrazine and carbendazim at 4 concentrations of effect on reprocduction (EC10, EC20, EC50 and EC90). Three biological replicates per treatment were used.
2012-05-27 | E-GEOD-33945 | biostudies-arrayexpress
Project description:Background: Molecular mechanisms of response to pesticides are scarce and information on such responses from soil invertebrates is almost inexistent. Enchytraeus albidus (Oligochaeta) is a standard soil ecotoxicology model species for which effects of many pesticides are known on survival, reproduction and avoidance behaviour. With the recent microarray development additional information can be retrieved on the molecular effects. Methodology/Principal Findings: Experiments were performed to investigate the transcription responses of E. albidus when exposed to three pesticides – dimethoate (insecticide), atrazine (herbicide) and carbendazim (fungicide) – in a range of concentrations that inhibited reproduction by 10%, 20%, 50% and 90% (EC10, EC20, EC50 and EC90, respectively). The goal of this study was to further identify key biological processes affected by each compound and if dose-related. All three pesticides significantly affected biological processes like translation, regulation of the cell cycle or general response to stress. Intracellular signalling and microtubule-based movement were affected by dimethoate and carbendazim whereas atrazine affected lipid and steroid metabolism (also by dimethoate) or carbohydrate metabolism (also by carbendazim). Response to DNA damage/DNA repair was exclusively affected by carbendazim. Conclusions: Changes in gene expression were significantly altered after 2 days of exposure in a dose-related manner. The mechanisms of response were comparable with the ones for mammals, suggesting across species conserved modes of action. The present results indicate the potential of using gene expression in risk assessment and the advantage as early markers.
2012-05-28 | GSE33945 | GEO
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Project description:Metaplastic breast carcinoma (MBC) is the most aggressive form of triple-negative cancer (TNBC), defined by the presence of “metaplastic” components of spindle, squamous, or sarcomatoid histology. The protein profiles underpinning the pathological subtypes and metastatic behavior of MBC are unknown. Using multiplex quantitative tandem mass tag-based proteomics we quantified 5,798 proteins in MBC, TNBC, and normal breast from 27 patients. MBC showed increased epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways compared to TNBC. MBC subtypes exhibited distinct upregulated profiles; translation and ribosomal events in spindle, inflammation and apical junctions in squamous, and extracellular matrix in sarcomatoid. Comparison of the proteomes of spindle MBC with MMTV-cre;Ccn6fl/fl spindle MBC tumors revealed a shared spindle-specific signature of 17 upregulated proteins involved in translation (e.g. RPL4,6,18, P3H1, PYCR1) and 19 downregulated proteins with roles in cell metabolism (e.g. ADH1B, ADH1C, LIPE, SOD1, FABP4). These data identify subtype specific MBC protein profiles providing biomarkers and therapeutic targets.
2020-04-22 | PXD014414 | Pride
Project description:We explored how Cas9-induced double-strand breaks (DSBs) on Ty1 produce genomic alterations in the diploid yeast Saccharomyces cerevisiae. Following Cas9 induction, we observed a significant elevation of chromosome rearrangements (large deletions and duplications), loss of heterozygosity (gene conversions, crossovers, and break-induced replication), and aneuploidy. Almost all of the chromosomal rearrangements reflect the repairing of DSBs at Ty1 elements by homologous recombination.
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Project description:Our data have revealed a correlation between the timing of ORC and MCM binding to origins and the timing of replication. We hypothesized that origins bind ORC during M with varying affinities, and that delays in ORC binding and pre-RC formation at late-firing origins result in low efficiencies due to these origins subsequently competing less effectively for limiting replication factors. We investigated if equalizing ORC binding results in changes in origin efficiencies. Because the increase in ORC binding occurs during M, we surmised that extending M might result in origins accumulating ORC more equally, leading to more equal distribution of pre-RC and pre-IC assembly among origins. As a consequence, early origins might become less efficient and late origins more efficient. To extend M in cells, we used the drug MBC (Carbendazim), which prevents microtubule polymerization and disrupts the mitotic spindle. Cells were then allowed to undergo S phase in the presence of BrdU, and labeled fragments were isolated by immunoprecipitation of genomic DNA and hybridized to Affymetrix tiling arrays. These results were compared to the replication profile of synchronized cells treated with HU but not with MBC, providing a control for normal origin efficiencies across the genome. This method allows the relative efficiency of origin usage genome-wide to be determined based on signal intensities from array hybridizations. Keywords: comparison between cells treated with a drug and normal cells
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