Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA214808 | ENA |
REPOSITORIES: ENA
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Project description:The monohaloacetic acids (monoHAAs) are generated as byproducts during the disinfection of drinking water and are cytotoxic, genotoxic, mutagenic, and teratogenic. Iodoacetic acid (IAA) toxicity was mitigated by antioxidants, suggesting the involvement of oxidative stress. Other monoHAAs may share a similar mode of action. Human oxidative stress and antioxidant defense gene arrays (SA biosciences) were used to evaluate changes in transcriptome profiles in the human intestinal epithelial cell line FHS 74 INT generated by three compounds, chloroacetic acid (CAA), bromoacetic acid (BAA) and IAA at two time points (30 min and 4 h).
2013-08-11 | GSE49698 | GEO
Project description:In this study we linked the biological end point of genomic DNA damage from our quantitative, comparative disinfection by-product (DBP) database, with toxicogenomic analysis using a Super Array RT2 Profiler™ PCR Array containing primers for 84 genes related to human DNA damage and repair and 84 genes whose expression level is indicative of stress and toxicity.
2009-04-08 | GSE15488 | GEO
Project description:The monohaloacetic acids (monoHAAs) are generated as byproducts during the disinfection of drinking water and are cytotoxic, genotoxic, mutagenic, and teratogenic. Iodoacetic acid (IAA) toxicity was mitigated by antioxidants, suggesting the involvement of oxidative stress. Other monoHAAs may share a similar mode of action. Human oxidative stress and antioxidant defense gene arrays (SA biosciences) were used to evaluate changes in transcriptome profiles in the human intestinal epithelial cell line FHS 74 INT generated by three compounds, chloroacetic acid (CAA), bromoacetic acid (BAA) and IAA at two time points (30 min and 4 h). Twelve samples were evaluated. Each treated sample was paired with a concurrent negative control (cells treated in medium only). Three technical repeats were included for each sample and Ct values were calculated from the average of the three repeats. Samples 1,2,and 3 were isolated from 30 min negative controls for CAA, BAA, and IAA respectively. Samples 4, 5, and 6 were isolated from cells treated for 30 min with CAA, BAA, and IAA respectivley. Samples 7, 8, and 9 were isolated from 4h negative controls for CAA, BAA, and IAA respectively. Samples 10, 11, and 12 were isolated from cells treated for 4 h with CAA, BAA and IAA respectively. Ct values were normalized against the average of the 5 housekeeping genes included in the array to generate M-NM-^TCt values. Fold changes for each gene were calculated as a ratio of 2^-M-NM-^TCttest / 2^-M-NM-^TCtcontrol.
2013-08-11 | E-GEOD-49698 | biostudies-arrayexpress
Project description:Although drinking water disinfection has proved to be an effective strategy to eliminate most waterborne pathogens, bacterial pathogens can still show disinfection tolerance in drinking water distribution systems (DWDSs), posing a great threat to drinking water safety and human health. Despite stress signals such as starvation and low temperature were reported to increase disinfection tolerance of E. coli, it is unclear whether the stress-induced disinfection tolerance was conserved in different bacterial species.
2020-10-10 | PXD021907 |
Project description:Human Cell Toxicogenomic Analysis of Bromoacetic Acid: A Regulated Drinking Water Disinfection By-product
| PRJNA115933 | ENA
Project description:Ozone has been proposed for water disinfection because it is more efficient than chlorine for killing microbes and results in much lower levels of carcinogenic trihalomethanes than does chlorination. Ozone leads to formation of hypobromous acid in surface waters with high bromine content and forms brominated organic by-products and bromate. The carcinogenicity and chronic toxicity of potassium bromate (KBrO3) [CAS:7758-02-3;CHEBI:32030] was studied in male B6C3F1 mice and F344/N rats to confirm and extend the results of previous work. Mice were treated with 0, 0.08, 0.4, or 0.8 g/L KBrO3 in the drinking water for up to 100 wk, and rats were provided with 0, 0.02, 0.1, 0.2, or 0.4 g/L KBrO3. Animals were euthanatized, necropsied, and subjected to a complete macroscopic examination. Selected tissues and gross lesions were processed by routine methods for light microscopic examination. The present study showed that KBrO3 is carcinogenic in the rat kidney, thyroid, and mesothelium and is a renal carcinogen in the male mouse, KBrO3 was carcinogenic in rodents at water concentrations as low as 0.02 g/L (20 ppm; 1.5 mg/kg/day). These data can be used to estimate the human health risk that would be associated with changing from chlorination to ozonation for disinfection of drinking water.
2006-11-14 | E-TOXM-21 | biostudies-arrayexpress
Project description:The process of drinking water disinfection forms compounds known as disinfection byproducts (DBPs). Studies have shown that DBPs can be harmful to human and animal health. Iodoacetic acid (IAA) is a non-regulated DBP that is cytotoxic and genotoxic to mammalian cells. In addition, IAA has been shown to be an ovarian toxicant in vitro and in vivo. However, the mechanisms of action underlying IAA toxicity on ovarian follicles in vivo remain unclear. In this study, we determined whether IAA exposure alters gene expression patterns in ovarian antral follicles in mice. Adult female CD-1 mice were dosed with water or IAA (10 or 500mg/L) in the drinking water for 35-40 days. Antral follicles were dissected from the ovaries based on size (220–400 μm). Sera were collected to measure estradiol levels. RNA-sequencing was applied to uncover the global gene expression of the antral follicles in response to IAA exposure. RNA-sequencing analysis identified 410 and 653 differentially expressed genes (DEGs) in the 10 and 500mg/L IAA treatment groups (FDR < 0.1), respectively, compared to controls. Gene Ontology Enrichment analysis showed that DEGs were involved with RNA processing and regulation of angiogenesis (10mg/L) and the cell cycle, cell division, and mitotic nuclear division (500mg/L). In addition, Pathway Enrichment analysis showed that DEGs were involved in the phosphatidylinositol 3-kinase and protein kinase B (PI3K-Akt) signaling pathway, gonadotropin-releasing hormone (GnRH) signaling pathway, estrogen signaling pathway, and insulin signaling pathway (10mg/L). In the 500mg/L group, Pathway Enrichment analysis showed that DEGs were involved in the oocyte meiosis signaling pathway, GnRH signaling pathway, and oxytocin signaling pathway. In addition, RNA-sequencing analysis identified 809 DEGs when comparing the 10 and 500mg/L IAA groups (FDR < 0.1). DEGs were related to ribosome, translation, mRNA processing, oxidative phosphorylation, chromosome, cell cycle, cell division, protein folding, platelet activation, and the oxytocin signaling pathway. Moreover, IAA exposure significantly decreased estradiol levels (500mg/L) in serum compared to control. This study identified key candidate genes and pathways involved in IAA toxicity that could help to further understand the molecular mechanisms of IAA toxicity in ovarian follicles.
2022-01-13 | GSE193409 | GEO
Project description:During oxidative stress, reactive oxygen species (ROS) can modify and damage cellular proteins. In particular, the thiol groups of cysteine residues can undergo reversible or irreversible oxidative post-translation modifications (PTMs). Identifying the redox-sensitive cysteines on a proteome-wide scale can provide insight into those proteins that act as redox sensors or become irreversibly damaged upon exposure to high levels of ROS. Aging is accompanied by oxidative stress, and oxygen-rich tissues such as the eye are particularly vulnerable because of its high energy demand and generation of ROS byproducts, which increases the risk for ocular disease. In this study, we profiled the redox proteome of the aging Drosophila eye to identify cysteine residues that are modified by age-associated ROS.
2023-04-27 | PXD036110 | Pride
Project description:Diabetes mellitus is a complex and heterogeneous disease that has β cell dysfunction at its core. Glucose toxicity affects pancreatic islets where it leads to β cell apoptosis. However, the role of JNK/β-catenin signaling pathway in glucotoxic β-cell apoptosis is poorly understood. To identify the potential genes whose expression changed in response to high glucose, we performed microarray analysis of gene expression in the RNAKT-15 cells for 48 h. Among the 41,000 genes tested, 1394 and 741 were twofold-upregulated and -downregulated, respectively. Genes involved in carbohydrate metabolism, cell cycle control, apoptotic process, and response to reactive oxygen species were upregulated. In contrast, genes involved in intracellular protein traffic, cell cycle, cell adhesion-mediated signaling, cell cycle control, response to reactive oxygen species, and apoptotic process were downregulated under high glucose-treated RNAKT-15 cells.
2015-12-21 | GSE76189 | GEO
Project description:Chlorination–derived byproducts of the emerging contaminant metformin, such as 3,3-CDTA and NCDC, occurring in global waters are toxic to biota, be it from bacteria to mice. However, the underlying toxicological mechanisms remain unknown. Here, we explored the toxicological effects and underlying molecular mechanisms of 3,3-CDTA and NCDC at milligram levels using Escherichia coli as a model organism. Compared with metformin (>300 mg/L), 3,3-CDTA and NCDC exerted stronger toxicity to E. coli with the 4-h IC50 of 2.97 mg/L and 75.7 mg/L, respectively. Both byproducts disrupted E. coli cellular structures and components, decreased membrane potential and adenosine triphosphate (ATP) biosynthesis, and produced excessive reactive oxidative species (ROSs), superoxide dismutase (SOD), and catalase. Proteomics analysis and molecular docking not only supported these biomarker responses in the byproduct-treated E. coli and indicated possible the damage of DNA/RNA process but also presented a novel insight into their toxicological and detoxification effects at the proteome level. Therefore, the mechanistically toxicological effects by which NCDC and 3,3-CDTA are toxic were ascribed to membrane disruption, oxidative stress, and abnormal protein expression. This study discusses the first toxicological effects of chlorination–derived metformin byproducts in E. coli and broadens understanding of the toxic effects and transformation risks of metformin throughout its entire life process.
2023-10-17 | PXD045084 | Pride