Similar Datasets
Project description:24 chemicals exposure to hESCs at different doses and time points
| PRJNA777904 | ENA
Project description:Environmental chemicals such as bisphenol A (BPA) are thought to contribute to carcinogenesis through their endocrine-disrupting effects. However BPA replacement chemicals are structurally similar, and little data exist describing their effects on the human body and environment. We established non-malignant human mammary organoid cultures to investigate the effects of BPA replacement chemicals on organoid morphology and protein abundance. At low-nanomolar doses, replacement chemicals, in particular BPS, induced branching and disrupted the organized mammary organoid architecture. BPS exposure likely alters mammary cell-type proportions and induces branching of predominately myoepithelial cells. Treatment with different replacement chemicals resulted in distinct proteomic changes. BPS exposure induced Cdc42-interacting protein 4 (CIP4), a protein known to support invadopodia formation and mesenchymal phenotypes. Our study provides evidence that replacement bisphenols have pro-tumorigenic effects on mammary morphology and the proteome, highlighting the necessity of comprehensive studies to evaluate the potential harm of replacement chemicals.
2021-06-11 | MSV000087617 | MassIVE
Project description:In this study we examined transcriptional responses to 29 ToxCast chemicals in dose-response format. The chemicals were selected because in vitro transcriptional effects could be extrapolated to in vivo effects including liver cancer and steatosis incidences using in vitro to in vivo extrapolation.
2020-03-24 | GSE147379 | GEO
Project description:BackgroundRegulatory toxicity values used to assess and manage chemical risks rely on the determination of the point of departure (POD) for a critical effect, which results from a comprehensive and systematic assessment of available toxicity studies. However, regulatory assessments are only available for a small fraction of chemicals.ObjectivesUsing in vivo experimental animal data from the U.S. Environmental Protection Agency's Toxicity Value Database, we developed a semiautomated approach to determine surrogate oral route PODs, and corresponding toxicity values where regulatory assessments are unavailable.MethodsWe developed a curated data set restricted to effect levels, exposure routes, study designs, and species relevant for deriving toxicity values. Effect levels were adjusted to chronic human equivalent benchmark doses (BMDh). We hypothesized that a quantile of the BMDh distribution could serve as a surrogate POD and determined the appropriate quantile by calibration to regulatory PODs. Finally, we characterized uncertainties around the surrogate PODs from intra- and interstudy variability and derived probabilistic toxicity values using a standardized workflow.ResultsThe BMDh distribution for each chemical was adequately fit by a lognormal distribution, and the 25th percentile best predicted the available regulatory PODs [R2≥0.78, residual standard error (RSE)≤0.53 log10 units]. We derived surrogate PODs for 10,145 chemicals from the curated data set, differentiating between general noncancer and reproductive/developmental effects, with typical uncertainties (at 95% confidence) of a factor of 10 and 12, respectively. From these PODs, probabilistic reference doses (1% incidence at 95% confidence), as well as human population effect doses (10% incidence), were derived.DiscussionIn providing surrogate PODs calibrated to regulatory values and deriving corresponding toxicity values, we have substantially expanded the coverage of chemicals from 744 to 8,023 for general noncancer effects, and from 41 to 6,697 for reproductive/developmental effects. These results can be used across various risk assessment and risk management contexts, from hazardous site and life cycle impact assessments to chemical prioritization and substitution. https://doi.org/10.1289/EHP11524.
| S-EPMC10056221 | biostudies-literature
Project description:We investigated the role of canonical WNT signaling in mesoderm and hematopoietic development from human embryonic stem cells (hESCs) using a recombinant human protein-based differentiation medium (APEL). In contrast to prior studies using less defined culture conditions, we found that WNT3A alone was a poor inducer of mesoderm. However, WNT3A synergized with BMP4 to accelerate mesoderm formation, increase embryoid body size, and increase the number of hematopoietic blast colonies. Interestingly, inclusion of WNT3A or a GSK3 inhibitor in methylcellulose colony-forming assays at 4 days of differentiation abrogated blast colony formation but supported the generation of mesospheres that expressed genes associated with mesenchymal lineages. Mesospheres differentiated into cells with characteristics of bone, fat, and smooth muscle. These studies identify distinct effects for WNT3A, supporting the formation of hematopoietic or mesenchymal lineages from human embryonic stem cells, depending upon differentiation stage at the time of exposure.
| S-EPMC3757745 | biostudies-literature
Project description:Most studies have analysed the effects of high dose radiation such as atomic bomb survivors in Japan, people exposed during the Chernobyl nuclear accident, patients undergoing radiation therapy, uranium miners, etc. However, it has been difficult to measure and assess the risk of cancer in people exposed to lower doses of ionising radiation, such as the people living at high altitudes, who are exposed to more natural background radiation from cosmic rays than people at sea level. We measured the genomic response to X-ray ionising radiation (10 cGy and 100 cGy) in a skin tissue model to compare the effects of low and high dose ionising radiation at different time points. The microarray data was then analysed using state-of-the art “upside-down pyramid” computational systems biology methods to identify genes contributing to the difference in the response to the different radiation doses.
2012-02-01 | GSE29344 | GEO
Project description:Environmental chemicals exposure are one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans.The discovery of early and sensitive biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. In the present study, we studied the dynamic changes in microRNAs (miRNAs) expression and explored the potential mechanistic role of miRNAs in rat liver treated with TAA at multiple doses and time points. Sprague-Dawley rats were administrated with TAA at three doses [low (4.5 mg/kg), middle (15mg/kg) and high (45mg/kg)] and four repeated treatment durations (3-, 7-, 14- and 28-days). Expressions of miRNAs in livers were profiled using next generation sequencing and analyzed. Overall, 330 unique differentially expressed miRNAs (DEMs) were identified in the entire TAA-treatment course. Of these, 129 DEMs were found significantly enriched for the “liver cancer” annotation. These results were further complemented by pathway analysis in which “Molecular Mechanisms of Cancer”, “p53-”, “TGF-β-”, “MAPK-” and “Wnt-signaling” were significantly enriched in most TAA-treatment conditions. Two miRNAs (rno-miR-34a-5p and rno-miR-455-3p) out of 48 DEMs (common across all the treatment conditions) were identified to be early and sensitive biomarkers for TAA-induced hepatocarcinogenicity. Upregulation of rno-miR-34a-5p was further confirmed by qPCR. These findings reveal the critical role of miRNAs in the mechanisms underlying hepatocarcinogenesis and potential application for human risk assessment. Most importantly, rno-miR-34a-5p is the most suitable early and sensitive biomarker for TAA-induced hepatocarcinogenesis due to its consistent elevation during the entire treatment course.
2017-06-23 | GSE87446 | GEO
Project description:To determine what genes are affect to the reduction in mutation frequency by 500 µGy gamma irradiation of Drosophila melanogaster. The strain is w[1118] (a loss of function mutant of compound eye pigment gene white with Canton-S background). Experiment Overall Design: 15 samples are analyzed. The control and four time course (5, 30, 60 and 90min), 3 Biological rep. (A to C).
2008-03-13 | E-GEOD-9552 | biostudies-arrayexpress
Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. The objective of this research is to determine genomic and proteomic responses in the model nematode C. elegans to exposures to representatives of several classes of toxic industrial chemicals/materials (TICs/TIMs). A total of 3 chemicals (acrylamide, cadmium chloride, and mercuric chloride) were used in these experiments. Affymetrix GeneChip for C. elegans was used to examine genome-wide responses in the 19,000+ genes of this model organism.
2012-11-28 | GSE42592 | GEO
Project description:Schistosomiasis, caused by infection with Schistosoma trematode parasites, is one of the deadliest neglected tropical diseases in the world. The Schistosoma lifecycle involves the miracidia infection of an intermediate molluscan host, such as Biomphalaria glabrata. Dispersing B. glabrata attractant chemicals has been considered a method of minimising host infections. The attractiveness of B. glabrata is known to be reduced following infection; however, it remained unclear how the duration of infection affects attractiveness. Identifying excretory-secretory proteins (ESPs) abundant in attractive snail conditioned water (SCW) may facilitate the identification of attractants. This study obtained SCW ESPs from naïve snails and at different time-points post-miracidia exposure (PME; 16h-, 1 week, 2 weeks and 3 weeks), to identify those ESPs mediating Schistosome mansoni miracidia behavioural changes. The ESPs were quantitatively identified from all SCW samples using a label-free proteomic method and genome-derived protein databases of B. glabrata and S. mansoni. We found that changes in miracidia behaviour were similar upon exposure to naïve and 3W-PME SCW, including increased circling and quantity of miracidia in the field of view. Of the ESPs identified, 21 were shared in SCW of naïve and 3W-PME, and considered attractant candidates, including acetylcholine-binding protein and immune-related proteins such as biomphalysins and thioester-containing protein 1. Some biological processes were exclusive to attractant candidates, including obsolete pathogenesis and transmembrane transport activity. This suggests that compromised production of these proteins may diminish host attractiveness to miracidia. Additionally, several immune proteins were identified exclusively at 16-PME and 1W-PME, providing further information into changing B. glabrata immune responses throughout infection. These findings provide a list of attractant candidates to potentially decrease B. glabrata infection and minimise schistosomiasis.
2022-10-03 | PXD031989 | Pride