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A Hightroughput Approach for Screening Potential Green Plasticizers Using A Human Prostate Cell Line [set2]

ABSTRACT: The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility. Animal studies have shown that phthalates can trigger cellular events associated with the onset of prostatic diseases. There is increasing interest in developing safe alternative plasticizers to phthalates. Many potential candidates were recently reported, and their mechanisms of action on prostatic cells warrant investigation. The goal of this study was to evaluate the toxicity of four families of chemicals that are candidate plasticizer using a non-cancerous human prostate cell line, PNT1A. These candidate plasticizers were compared to diethylhexyl phthalate (DEHP), its main bioactive metabolite monohexylethyl phthalate (MEHP), and a current “green” plasticizer that is being used increasingly, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), using a combination of classical (MTT) and high throughput techniques (HCS, microarray). High content screening provided additional information about cell counts and range of parameters related to cell function. The incorporation of gene expression studies revealed that several of the compounds tested in this study had an effect on cellular functions, even those that had not shown any effect with the other assays. While DINCH was found to have wide ranging effects, we show that candidate plasticizers of the dibenzoate family have no effects on metabolic activity, cellular morphology, cellular proliferation or gene expression in PNT1A cells. Candidate plasticizers of the succinate family had an effect only at the gene expression level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67397 | GEO | 2021/05/15

REPOSITORIES: GEO

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A Hightroughput Approach for Screening Potential Green Plasticizers Using A Human Prostate Cell Line [set3]

Project description:The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility. Animal studies have shown that phthalates can trigger cellular events associated with the onset of prostatic diseases. There is increasing interest in developing safe alternative plasticizers to phthalates. Many potential candidates were recently reported, and their mechanisms of action on prostatic cells warrant investigation. The goal of this study was to evaluate the toxicity of four families of chemicals that are candidate plasticizer using a non-cancerous human prostate cell line, PNT1A. These candidate plasticizers were compared to diethylhexyl phthalate (DEHP), its main bioactive metabolite monohexylethyl phthalate (MEHP), and a current “green” plasticizer that is being used increasingly, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), using a combination of classical (MTT) and high throughput techniques (HCS, microarray). High content screening provided additional information about cell counts and range of parameters related to cell function. The incorporation of gene expression studies revealed that several of the compounds tested in this study had an effect on cellular functions, even those that had not shown any effect with the other assays. While DINCH was found to have wide ranging effects, we show that candidate plasticizers of the dibenzoate family have no effects on metabolic activity, cellular morphology, cellular proliferation or gene expression in PNT1A cells. Candidate plasticizers of the succinate family had an effect only at the gene expression level.

2021-05-15 | GSE67398 | GEO

A Hightroughput Approach for Screening Potential Green Plasticizers Using A Human Prostate Cell Line [set1]

Project description:The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility (Burden et al. 2006 and references therein). Animal studies have shown that phthalates can trigger cellular events associated with the onset of prostatic diseases. There is increasing interest in developing safe alternative plasticizers to phthalates. Many potential candidates were recently reported, and their mechanisms of action on prostatic cells warrant investigation. The goal of this study was to evaluate the toxicity of four families of chemicals that are candidate plasticizer using a non-cancerous human prostate cell line, PNT1A. These candidate plasticizers were compared to diethylhexyl phthalate (DEHP), its main bioactive metabolite monohexylethyl phthalate (MEHP), and a current “green” plasticizer that is being used increasingly, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), using a combination of classical (MTT) and high throughput techniques (HCS, microarray). High content screening provided additional information about cell counts and range of parameters related to cell function. The incorporation of gene expression studies revealed that several of the compounds tested in this study had an effect on cellular functions, even those that had not shown any effect with the other assays. While DINCH was found to have wide ranging effects, we show that candidate plasticizers of the dibenzoate family have no effects on metabolic activity, cellular morphology, cellular proliferation or gene expression in PNT1A cells. Candidate plasticizers of the succinate family had an effect only at the gene expression level.

2021-05-15 | GSE67396 | GEO

Toxicogenomic Screen of Replacements for bis(2-ethylhexyl) phthalate (DEHP) Using the Immortalized TM4 Sertoli Cell Line

Project description:Phthalate plasticizers are being phased out of consumer products because of their endocrine disrupting properties. This has resulted in a need to find safe alternatives that can plasticize polyvinyl chloride (PVC) while being inexpensive and biodegradable. We aim to study the toxicogenomic profile of mono-(2-ethylhexyl) phthalate (MEHP, the active metabolite of bis(2-ethylhexyl) phthalate, DEHP), the commercial plasticizer 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), and three plasticizers in development (1,4 butanediol dibenzoate (BDB), dioctyl succinate (DOS), and dioctyl maleate (DOM)) using the immortalized TM4 Sertoli cell line. Each sample contains four biological replicates except for DOS that contains three. The control is 1.0% DMSO as this was the vehicle used to solubilize the test compounds.

2015-08-06 | E-GEOD-66812 | biostudies-arrayexpress

Toxicogenomic Screen of Replacements for bis(2-ethylhexyl) phthalate (DEHP) Using the Immortalized TM4 Sertoli Cell Line

2015-08-06 | GSE66812 | GEO

The effects of phthalates on S. tropicalis development

Project description:Phthalates are added to polymers in order to increase their flexibility, but leach out of the matrix. Given that these plasticizers are mainly found in water bound to particles, aquatic species are exposed to phthalates. Silurana tropicalis eggs were exposed to high concentrations of three pththalates: dicyclohexyl phthalate (DCHP; 19 mg/L), dimethyl phthalate (DMP; 34 mg/L), and monomethyl phthalate (MMP; 1500 mg/L), along to their respective controls: 0.82% DMSO for DCHP, and water controls for DMP and MMP. The exposure lasted 3 days during embryogenesis. Four pooled of 10 larvae were sampled per treatment and analyzed for gene expression changes using a microarray approach.

2014-07-31 | GSE57675 | GEO

THP-1 cells treated with plasticizer DINCH and metabolite MINCH

Project description:Since 2008, the consumption of the plasticizer bis (2-ethylhexyl) phthalate (DEHP) in the manufacture of plastic products has been restricted due to several adverse health effects. 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) is increasingly used as a harmless substituent for DEHP. However, the structural similarity to DEHP and first studies demonstrating adverse effects on reproduction and metabolism in rats, suggest that DINCH may act adverse on human health. Still, there is a lack of studies on the biological effects of DINCH, especially in the immune system, which is in constant communication with other tissues and thus crucial for maintaining a functional organism. Here we aimed to investigate the effects of DINCH and its naturally occurring biotransformation product monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) on the innate immune response. Human THP-1 macrophages were exposed to DINCH and MINCH in a concentration range of 10 nM to 10 μM for 4 h, 16 h and 24 h in the presence of LPS.

2022-01-10 | PXD027744 | Pride

Effects of in utero and lactational exposure to new generation green plasticizers on adult male rats: a comparative study with di(2-ethylhexyl) phthalate

Project description:Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, is a ubiquitous environmental pollutant and may act as an endocrine disruptor. Early life exposures to DEHP may result in anti-androgenic effects, impairing the development of the male reproductive tract. However, data on the long-lasting consequences of such DEHP exposures on adult male reproductive function are still rare and discrepant. Previously, we identified two novel plasticizers, 1,4 butanediol dibenzoate (BDB) and dioctyl succinate (DOS), as potential substitutes for DEHP that did not reproduce classically described endocrine disrupting phenotypes in prepubertal male offspring after maternal exposure. Here, we investigated the consequences of in utero and lactational exposure to BDB and DOS on adult male rat reproductive function in a comparative study with DEHP and a commercially available alternative plasticizer, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH). Timed pregnant Sprague-Dawley rats were gavaged with vehicle or a test chemical (30 or 300 mg/kg/day) from gestation day 8 to postnatal day 21. While DEHP exposure (300 mg/kg/day) significantly increased epididymal weight in the adult, exposure to DINCH, BDB or DOS did not affect reproductive organ weights, steroid levels or sperm quality. Using a toxicogenomic microarray approach, we found that adult testicular gene expression was affected by exposure to the higher dose of DEHP; transcripts such as Nr5a2, Ltf or Runx2 were significantly downregulated, suggesting that DEHP was targeting estrogen signaling. Lesser effects were observed after treatment with either DINCH or BDB. DOS exposure did not produce such effects, confirming its potential as a responsible substitute for DEHP. The data deposited correspond to testicular gene expression in 90 day-old Sprague-Dawley rats after exposure to CORN OIL and 30 or 300 mg/kg/day DEHP, DINCH, BDB or DOS from gestational day 8 to post-natal day 21

2018-02-14 | GSE110553 | GEO

Effects of DEHP on the hepatic expression of a selection of mouse genes related to nuclear receptor signaling.

Project description:Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this study we investigated potential mechanisms underlying the impact of di-(2-ethylhexyl)-phthalate (DEHP) on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARÎ± targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and on the Rev-erbÎ± pathway that senses endogenous heme level. Keywords: Treatment effect One-color macroarrays, 4 experimental conditions: Control mice (vehicle treated), mice treated with di-(2-ethylhexyl)-phthalate (DEHP) at 30 mg/kg/day (D30), 180 mg/kg/day (D180) or 1100 mg/kg/day (D1100) for 14 days, Biological replicates: 6 controls, 4 D30, 4 D180, 5 D1100, One replicate per array

2010-05-05 | E-GEOD-14629 | biostudies-arrayexpress

Role of PPARalpha in the effects of DEHP on the hepatic expression of a selection of mouse genes

Project description:Role of PPARalpha in the effects of DEHP on the hepatic expression of a selection of mouse genes related to nuclear receptor signaling. Di-(2-ethylhexyl)-phthalate (DEHP), a widely used plasticizer, is detected in consumerâs body fluids. Contamination occurs through environmental and food chain sources. In mouse liver, DEHP activates the peroxisome proliferator-activated receptor alpha (PPARalpha) and regulates the expression of its target genes. Several in vitro investigations support the simultaneous recruitment of additional nuclear receptor pathways. We investigated, in vivo, the hepatic impact of low doses of DEHP on PPARalpha activation, and the putative activation of additional signalling pathways. Wild-type and PPARalpha-deficient mice were exposed to different doses of DEHP. Gene expression profiling delineated the role of PPARalpha and revealed a PPARalpha-independent regulation of several prototypic Constitutive Androstane Receptor (CAR) target genes. This finding demonstrates that CAR also represents a transcriptional regulator sensitive to phthalates. CAR-mediated effects of DEHP provide a new rationale for most endpoints of phthalates toxicity described previously, including endocrine disruption, hepatocarcinogenesis and the metabolic syndrome. Keywords: Treatment effect One-color macroarrays, 6 experimental conditions: Wild type (WT) and PPARalpha-deficient mice (PPAR) were treated with vehicle (Ctrl) or with di-(2-ethylhexyl)-phthalate (DEHP) at 20 mg/kg/day (D20) or 200 mg/kg/day (D200) for 21 days, Biological replicates: 10 for each group, One replicate per array

2010-05-22 | E-GEOD-14920 | biostudies-arrayexpress

Effects of DEHP on the hepatic expression of a selection of mouse genes related to nuclear receptor signaling.

Project description:Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this study we investigated potential mechanisms underlying the impact of di-(2-ethylhexyl)-phthalate (DEHP) on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARα targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and on the Rev-erbα pathway that senses endogenous heme level. Keywords: Treatment effect

2009-02-19 | GSE14629 | GEO

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