Human cell toxicogenomic analysis links reactive oxygen species to the toxicity of monohaloacetic acid drinking water disinfection byproducts
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49698 | GEO | 2013/08/11
SECONDARY ACCESSION(S): PRJNA214808
REPOSITORIES: GEO
Similar Datasets
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: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:Comparison of off target alkylation using chloroacetamide (CAA) and iodoacetamide (IAA). The peptide preparation was performed side by side, following identical methods except the alkylation treatment with either IAA or CAA. None of the comparison of off-targets on between IAA and CAA showed a significant difference. The overall off-target level for both reagents was relatively low (< 0.1%) and the off-target rate on lysine residues was even lower (0.045% for IAA and 0.051% for CAA).
2024-07-31 | MSV000095495 | MassIVE
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: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:In this study, we systematically evaluated reduction and alkylation of proteins using three reducing agents (DTT, TCEP, and BME) in combination with four alkylation agents (IAA, IAC, AA, and CAA). We tested these conditions using strong anion exchange (SAX) fractionated in-solution digests and in-gel digested fractions of samples enriched for cytosolic proteins of HeLa cells. We analyzed the data using Proteome Discoverer 2 in combination with the MASCOT search engine with different combinations of variable and fixed modifications as well as error tolerant and mass tolerant searches. Furthermore, we compared IAA and AA alkylated samples by dimethyl labeling and performed multi stage activation triggered by the neutral loss of alkylated methionine side chains. This led to the identification of prominent offside alkylation due to iodine containing reagents at tyrosine, serine, threonine, histidine, lysine, methionine, aspartic and glutamic acid as well as the peptide N-terminus with varying abundances based on the reduction and alkylation reagents used.
2017-05-30 | PXD005183 | Pride
Project description:Human cell toxicogenomic analysis links reactive oxygen species to the toxicity of monohaloacetic acid drinking water disinfection byproducts
| PRJNA214808 | ENA
Project description:Disinfection by-products (DBPs) exposure has been linked to multiple adverse health outcomes. However, the molecular initiating events by which DBPs induce their toxicities remains unclear. Herein we combined reporter cell lines and activity-based protein profiling (ABPP) chemical proteomics to identify protein targets of six haloacetic acids (HAAs) and haloacetamides (HAMs), on the proteome-wide level. While HAAs and HAMs had similar cytotoxicities, when compared to controls, the later has 12.5 times greater Nrf2-mediated oxidative stress response, demonstrating their distinct toxicity pathways. ABPP on crude cell lysates suggested that nonspecific proteome thiol reactivity correlates with cytotoxicity. Interestingly, live cell ABPP results revealed class-specific proteins attacked by HAMs or HAAs. Subsequent proteomics analysis identified >100 unique targets per DBP. HAMs showed preferential reactivity towards disulfide oxidoreductase enzymes, accounting for their stronger Nrf2 responses. To further probe alkylation mechanisms, we directly monitored protein adducts and identified 120 and 37 unique peptides with IAM and IAA adducts, respectively. Of the later we confirmed glyceraldhye-3-phosphate dehydrogenase (GAPDH) as a key target of IAA, specifically attacked at the catalytic Cys 152. This is the first study reporting the distinct cellular protein targets of HAAs and HAMs on the proteome-wide level, which highlights their different toxicity pathways despite their similar structures.
2020-11-11 | PXD018825 | Pride
Project description:Lameness due to femoral head separation (FHS) is a production and welfare issue in commercial poultry. FHS is an idiopathic disorder, which is attributed to a myriad of factors but in order to improve bone health, broiler breeders must be prognosed for disease susceptibility and selected against FHS using biomarkers. Proteins from plasma of blood, which can be obtained using minimally invasive methods represent an ideal, rich source of biomarkers which might be different in susceptible or affected birds. The peptide and proteins in plasma of healthy (HLTH) and affected birds (FHS) were compared using Matrix assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS) and Liquid chromatography and tandem mass spectrometry (LC-MS/MS). The peptide profile of HLTH and FHS were compared using ClinPro tools and the differentially expressed peptides were isolated by Reverse phase liquid chromatography fractionation (C18-RP-HPLC) and identified using peptide mass fingerprinting. Peptides derived from fibrinogen precursor and fetuin were reduced in FHS birds. Based on the proteomic analysis, proteins such as Gallinacin 10, Apolipoprotein A-1 and Hemoglobin chains are elevated in FHS while Alpha 1-acid glycoprotein is reduced in FHS birds. Our study shows that bodyweight, lipid profile and the above mentioned proteins could be useful as a biomarker for improvement of bone health. These proteins indicate that blood lysis, antimicrobial defense and lipid disorder but lack of an inflammatory response might be consequential to FHS.
2016-08-09 | PXD003292 | Pride
Project description:Water disinfection byproducts increase natural transformation rates of environmental DNA in Acinetobacter baylyi ADP1
| PRJEB28698 | ENA