Influence of Water Chemistry on Toxicogenomics of Chronic Lead Toxicity to the Fathead Minnow (Pimephales promelas)
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ABSTRACT:
ORGANISM(S): Pimephales promelas
PROVIDER: GSE8404 | GEO | 2008/04/07
SECONDARY ACCESSION(S): PRJNA101459
REPOSITORIES: GEO
Similar Datasets
Project description:Despite major successes in reducing the risks of lead (Pb) exposure over the past few decades, two issues of considerable importance remain unresolved: (1) how differences in water chemistry influence acute and chronic Pb toxicity, and (2) the elucidation of specific toxic mechanisms and modes of action (MOA). To more clearly define the water chemistry parameters mediating Pb toxicity we evaluated the effects of hardness (as CaSO4) and DOC (as humic acid (HA)) during chronic (150d) exposures to the fathead minnow (Pimephales promelas). Traditional toxicological endpoints were examined alongside gene expression analyses to help clarify the underlying mechanisms and MOA of Pb toxicity and to identify robust molecular markers of exposure and effect. Keywords: time course, chronic lead (Pb) exposure To analyze the gene expression responses to low-level Pb exposures fish were exposed +/- Pb in low ionic strength base water and fish collected at 2d, 4d, 10d, and 30d for microarray analysis. Equal amounts of RNA from all no lead controls were pooled (18 fish total for 2d & 4d exposures; 12 fish total for 10d & 30d exposures) as reference samples for hybridization with each of 3 separate biological replicate pools (6 fish total for 2d & 4d exposures; 4 fish total for 10d & 30d exposures) of RNA from age-matched, lead-exposed fish. Each pair of hybridizations was repeated with dye-swaps. Additional repeats were performed for various arrays to ensure quality of data obtained from initial hybridization.
2008-04-06 | E-GEOD-8404 | biostudies-arrayexpress
Project description:Plastic particles in water environment can adsorb heavy metals, leading to combined toxicity to aquatic organisms. However, current conclusions are mostly obtained based on cell population-average responses. Heterogeneity effects among cell populations in aquatic organisms remain unclear. This study analyzed the heterogeneity effects of 200 μg/L 100 nm polystyrene nanoplastics (PS-NPs), 50 μg/L lead (Pb), and their combined exposures on zebrafish intestine cells by single-cell RNA sequencing.A total of 38640 cells in the zebrafish intestine was obtained and identified as seven cell populations, including enterocytes, macrophages, neutrophils, B cells, T cells, enteroendocrine cells, and goblet cells.Co-exposure of PS-NPs and Pb caused similar transcriptome profiles with PS-NPs exposure in macrophages, which changed immunological recognition processes. The Pb exposure influenced the macrophages by direct cytotoxicity. However, the Pb alone and combined exposures induced similar modes of action in the enterocytes, including the generation of oxidative stress and abnormal lipid metabolism.
2022-02-25 | GSE165888 | GEO
Project description:Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physico-chemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes co-varied with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multi-level effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants. The hybridization design was a universal reference design (a mixture of aliquots from control and exposed samples), which is recommended when class discovery is the main purpose of the experiment. One of the three biological replicates of each exposure condition was labeled with one dye, the remaining two samples were labeled with the second dye.
2012-02-01 | E-GEOD-29864 | biostudies-arrayexpress
Project description:Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physico-chemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes co-varied with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multi-level effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants. The hybridization design was a universal reference design (a mixture of aliquots from control and exposed samples), which is recommended when class discovery is the main purpose of the experiment. One of the three biological replicates of each exposure condition was labeled with one dye, the remaining two samples were labeled with the second dye.
2012-02-01 | E-GEOD-29867 | biostudies-arrayexpress
Project description:Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physico-chemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes co-varied with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multi-level effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants. The hybridization design was a universal reference design (a mixture of aliquots from control and exposed samples), which is recommended when class discovery is the main purpose of the experiment. One of the three biological replicates of each exposure condition was labeled with one dye, the remaining two samples were labeled with the second dye.
2012-02-01 | E-GEOD-29862 | biostudies-arrayexpress
Project description:Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physico-chemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes co-varied with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multi-level effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants. The hybridization design was a universal reference design (a mixture of aliquots from control and exposed samples), which is recommended when class discovery is the main purpose of the experiment. One of the three biological replicates of each exposure condition was labeled with one dye, the remaining two samples were labeled with the second dye.
2012-02-01 | E-GEOD-29856 | biostudies-arrayexpress
Project description:Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physico-chemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes co-varied with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multi-level effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants. The hybridization design was a universal reference design (a mixture of aliquots from control and exposed samples), which is recommended when class discovery is the main purpose of the experiment. One of the three biological replicates of each exposure condition was labeled with one dye, the remaining two samples were labeled with the second dye.
2012-02-01 | E-GEOD-29854 | biostudies-arrayexpress
Project description:Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physico-chemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes co-varied with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multi-level effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants. The hybridization design was a universal reference design (a mixture of aliquots from control and exposed samples), which is recommended when class discovery is the main purpose of the experiment. One of the three biological replicates of each exposure condition was labeled with one dye, the remaining two samples were labeled with the second dye.
2012-02-01 | E-GEOD-29857 | biostudies-arrayexpress
Project description:Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physico-chemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes co-varied with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multi-level effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants. The hybridization design was a universal reference design (a mixture of aliquots from control and exposed samples), which is recommended when class discovery is the main purpose of the experiment. One of the three biological replicates of each exposure condition was labeled with one dye, the remaining two samples were labeled with the second dye.
2012-02-01 | E-GEOD-29858 | biostudies-arrayexpress
Project description:Background: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. We isolate total RNA from 72 mouse whole blood samples. These included samples following a 2-week exposure to lead acetate trihydrate (untreated controls = 7; Low Pb 5ug/mL drinking water = 15; High Pb 50ug/mL drinking water = 15) and additional samples following a 2-week recovery period with plain drinking water (untreated controls = 7; Low Pb group = 15; High Pb group = 13).
2011-03-30 | E-GEOD-28261 | biostudies-arrayexpress