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A toxicogenomics approach to screen chlorinated flame retardants tris(2-chloroethyl) phosphate and tris(2-chloroisopropyl) phosphate for potential health effects

ABSTRACT: A toxicogenomics approach to screen chlorinated flame retardants tris(2-chloroethyl) phosphate and tris(2-chloroisopropyl) phosphate for potential health effects

PROVIDER: PRJNA430954 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6501990_1.fastq.gz	Fastqsanger.gz
	SRR6501990_2.fastq.gz	Fastqsanger.gz
	SRR6501981_1.fastq.gz	Fastqsanger.gz
	SRR6501981_2.fastq.gz	Fastqsanger.gz
	SRR6501991_1.fastq.gz	Fastqsanger.gz

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A toxicogenomics approach to screen chlorinated flame retardants tris(2-chloroethyl) phosphate and tris(2-chloroisopropyl) phosphate for potential health effects

Project description:Tris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2. We identified that compared to other flame retardants, TCEP and TCIPP had little cytotoxicity. Treatment with sub-cytotoxic concentrations of the two compounds revealed that both chemicals elicited similar effects; both compounds were found to affect genes involved in immune responses and steroid hormone biosynthesis, while also affecting xenobiotic metabolism pathways in a similar manner. Specifically for effects on immune responses, both compounds were shown to alter the expression of the receptor of the potent and pleiotropic complement component, C5a. Additionally, expression of genes encoding for effector proteins involved in the complement cascade along with other potent inflammatory regulators were found altered in response to TCEP and TCIPP, further emphasizing their potential effects on immune function. Taken together, given that TCIPP elicited similar effects compared to TCEP, and at lower concentrations, the potential health effects of TCIPP need to be further studied for a complete risk assessment of the compound.

2018-01-20 | GSE109463 | GEO

Gene expression changes of tris(2-chloroethyl)phosphate-induced in renal cortex of rats

Project description:This study is to develop a short term and highly accurate prediction method of renal carcinogenicity based on gene expression profile of rats administrated by carcinogens. We conducted 28 days-repeated dose experiments in male SD rats with tris(2-chloroethyl)phosphate, and the gene expression profiles of renal cortex were analyzed using custom microarrays.

2016-09-27 | GSE87270 | GEO

08 Chemical-induced gene expression changes in rat liver

Project description:Tris(2-Chloroethyl) Phosphate hydrochloride-induced gene expression changes in rat liver

2016-09-30 | GSE87143 | GEO

Expression data from HeLa cell treated with Tris(1,3-dichloro-2-propyl)phosphate

Project description:Tris(1,3-dichloro-2-propyl)phosphate is widely used in consumer products as a flame retardant. Humans are often exposed to this compound. However, the molecular mechanisms of the compound`s adverse effects are still unclear. We address the molecular and cellular mechanisms underlying tris(1,3-dichloro-2-propyl)phosphate effects on HeLa cells. Here RNA-Seq analysis was performed to identify distinct classes of up- or down-regulated genes and their connections to different metabolic pathways.

2020-05-27 | GSE147560 | GEO

Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq.

Project description:Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels. Over-representation and gene set enrichment analysis corresponded well and revealed that TBOEP treatments resulted in an upregulation of genes involved in protein and energy metabolism, along with DNA replication. Such increases in cell and macromolecule metabolism could explain the increase in mitochondrial activity at lower TBOEP concentrations. In addition, TBOEP affected a wide variety of biological processes, the most notable one being the general stress response, wound healing. Finally, TBOEP showed effects on steroid hormone biosynthesis and activation, regulation, and potentiation of immune responses, in agreement with other studies. As such, this study is the first study investigating genome-wide changes in gene transcription in response to TBOEP in human cells.

2018-01-12 | GSE109072 | GEO

Project description:Tris (2-chloroethyl) phosphate degrading consortia sequencing

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Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq.

Project description:Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq.

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Effects of organophosphate flame retardants on Atlantic cod liver cells

Project description:Organophosphorous flame retardants (PFRs) were first reported in the late 1970, and today they account for approximately 20 % of the total use of flame retardants in Europe. PFRs are found ubiquitously in the environment, including remote areas stretching from the Arctic to the Antarctic. Generally, similar levels of PFRs is observed between Arctic and more rural areas. The toxicity of PFRs varies depending on their chemical structure. The World Health Organization have reported LC50 values for mammals and aquatic organisms with high variation from 4.2 to 180 mg/L or 707 to 4700 mg/kg body weight, depending on substance and test species. However, little is known about the toxicity and physiological effects of PFRs to fish, particularly in the Arctic species. Hence, the objective of this study is to determine the effects of PFR exposure on hepatic gene expression patterns in Atlantic cod (Gadus morhua) using liver explants in vitro. Liver explants were exposed to 2-Ethylhexyl diphenyl phosphate (EHDPP), tris(2-chloroisopropyl)phosphate (TCPP), and a mixture of both EHDPP and TCPP for 0, 24 and 48 hours. Samples were analyzed for gene expresson profiling using RNAseq. RNAsequening results suggest that exposure to PFRs differentially expressed genes involved in xenobiotic metabolism. We did not observe any chemical-specific effects on gene expression patterns. However, temporal changes in gene expression were observed. Most of the differentially expressed genes (DE) in 24h exposed samples are related in xenobiotic metabolism, whereas in 48h samples DE genes belong to diverse physiological processes.

2017-12-31 | GSE103954 | GEO

Project description:Biotransformation of tris(2-chloroethyl) phosphate (TCEP) in sediment microcosms

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Expression data from HeLa cell treated with Tris(1,3-dichloro-2-propyl)phosphate

Project description:Expression data from HeLa cell treated with Tris(1,3-dichloro-2-propyl)phosphate

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