Perfluorinated compounds differentially affect steroidogenesis and viability in the human adrenocortical carcinoma (H295R) in vitro cell assay

Kraugerud, Marianne; Zimmer, Karin Elisabeth; Ropstad, Erik; Verhaegen, Steven

doi:10.1016/j.toxlet.2011.05.230

Cited by 69 publications

(34 citation statements)

References 36 publications

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“…There were some cases in which the results of hormone production and CYP19 gene expression were consistent with each other [29]. Kraugerud et al found that PFOS caused a numerically higher level of E2 followed by a concentration-response relationship, and E2 was significantly elevated at 600 mM PFOS [30]. These results were consistent with our finding that PFOS induced E2 production.…”

Section: Discussionsupporting

confidence: 91%

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

Huang

et al. 2012

Enviro Toxic and Chemistry

154

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Abstract-Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafishbased short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 mg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo. Environ. Toxicol. Chem. 2013;32:353-360. # 2012 SETAC

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Section: Discussionsupporting

confidence: 91%

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

Huang

et al. 2012

Enviro Toxic and Chemistry

154

View full text Add to dashboard Cite

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“…b-actin was used as an endogenous control to reflect the relative abundance of the target gene. Data were analyzed and were expressed as relative gene expression (fold increase) using the 2 -rrCt method (Kraugerud et al 2011). QRT-PCR was conducted in triplicate for each sample.…”

Section: Determination Of Blood Lipid Levelsmentioning

confidence: 99%

Inflammatory responses induced by fluoride and arsenic at toxic concentration in rabbit aorta

Niu

Sun

et al. 2012

Arch Toxicol

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Epidemiological and experimental studies have demonstrated the atherogenic effects of environmental toxicant arsenic and fluoride. Inflammatory mechanism plays an important role in the pathogenesis of atherosclerosis. The aim of the present study is to determine the effect of chronic exposure to arsenic and fluoride alone or combined on inflammatory response in rabbit aorta. We analyzed the expression of genes involved in leukocyte adhesion [P-selectin (P-sel) and vascular cell adhesion molecule-1(VCAM-1)], recruitment and transendothelial migration of leukocyte [interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)] and those involved in pro-inflammatory cytokines [interleukin-6 (IL-6)]. We found that fluoride and arsenic alone or combined increased the expression of VCAM-1, P-sel, MCP-1, IL-8, and IL-6 at the RNA and protein levels. The gene expressions of inflammatory-related molecules were attenuated when co-exposure to the two toxicants compared with just one of them. We also examined the lipid profile of rabbits exposed to fluoride and (or) arsenic. The results showed that fluoride slightly increased the serum lipids but arsenic decreased serum triglyceride. We showed that inflammatory responses but not lipid metabolic disorder may play a crucial role in the mechanism of the cardiovascular toxicity of arsenic and fluoride.

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“…In addition, the H295R model was used to evaluate modulation of steroidogenic hormone production by single polychlorinated biphenyl (PCB) congeners [23], emerging pollutants (e.g., perfluorinated compounds) [24], and pharmaceuticals [19,71]. It was also deployed to look at effects of estrogenic mycotoxin, zearalenone, and the metabolites, a-and b-zearalenol.…”

Section: Endocrine Disruption At Hormone-production Levelmentioning

confidence: 99%

“…Recent advances in cell biology and biotechnology have allowed development of a new generation of bioassays focused on hormonal nuclear receptor signaling [14][15][16][17][18] and steroidogenesis pathways [11,[19][20][21][22][23][24][25]. Some of these new bioassays are based on the ability to introduce specific properties and reporter genes into stable cellular systems.…”

Section: Introductionmentioning

confidence: 99%

“…Given the wide scope of potential working mechanisms and sites of action of EDCs, the review focuses on those bioassays measuring interference of EDCs with nuclear receptor signaling (see sub-section 2.1) or Has been applied to known food contaminants, either as single compound [20,23,24], or as mixtures [11,25] The hormone production (see sub-section 2.2), These mechanisms are very complementary and the bioassays and their use very well documented. We give attention to assays validated or being validated by control organizations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro bioassays for the study of endocrine-disrupting food additives and contaminants

Connolly

Ropstad

Verhaegen

2011

TrAC Trends in Analytical Chemistry

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Perfluorinated compounds differentially affect steroidogenesis and viability in the human adrenocortical carcinoma (H295R) in vitro cell assay

Cited by 69 publications

References 36 publications

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

Inflammatory responses induced by fluoride and arsenic at toxic concentration in rabbit aorta

In vitro bioassays for the study of endocrine-disrupting food additives and contaminants

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