Modification of gene expression in prostate cancer cells treated with Perfluorooctanoic acid
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE150655 | GEO | 2022/06/08
REPOSITORIES: GEO
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Project description:Perfluorooctanoic acid (PFOA) is one of the most used perfluorinated compounds in numerous applications and can be detected in environmental samples from around the globe. The aquatic environment is an important site for PFOA deposit. Nevertheless, the exact mode of action and its resulting toxicological effects on aquatic organisms remain largely unknown. To gain a more extensive understanding of the mode of action of teleost PFOA toxicity, transcriptomics, proteomics, biochemical parameters and reproduction were integrated in the present study. Male and female zebrafish were exposed to nominal concentrations of 0.1; 0.5 and 1 mg/l PFOA for 4 and 28 days resulting in an accumulation which was higher in males compared to females. These gender-related differences were likely caused by different elimination rates due to distinct hormone levels and differences in transport activity by solute carriers. The general mode of action of PFOA was believed to be an increase of the mitochondrial membrane permeability which caused effects on the electron transport system at the biochemical level and resulted in alterations of the oxidative phosphorylation, oxidative stress and apoptosis at the gene transcript and protein level. As a consequence, evidence for the replacement of the affected cells and organelles to sustain tissue homeostasis was found at the molecular level. The higher energy demand, due to these adverse effects, was provided by lowering the glycogen stores. Despite this increase in metabolic expenditure, no effects on reproduction were found indicating that the fish seemed to cope with exposure to the tested concentrations of PFOA. Adult zebrafish (Danio rerio) were exposed to nominal concentrations of 0mg/l; 0.1mg/l; 1mg/l PFOA (perfluorooctanoic acid) for 28 days. Three different 25 litre aquaria per exposure concentration were used resulting in 3 biological replicates with each aquarium containing 8 male and 8 female zebrafish. The livers of 6 male fish and 6 female fish were pooled separately and snap frozen in liquid nitrogen. A reference sample was made by pooling equal amounts of RNA from all samples. A carriage wheel design was used in which all samples were connected to the reference sample and the main contrasts of interest were made directly on the same microarrays as frequently as possible. This design resulted in technical triplicates of each sample.
2013-07-20 | E-GEOD-19908 | biostudies-arrayexpress
Project description:Perfluorooctanoic acid (PFOA) is one of the most used perfluorinated compounds in numerous applications and can be detected in environmental samples from around the globe. The aquatic environment is an important site for PFOA deposit. Nevertheless, the exact mode of action and its resulting toxicological effects on aquatic organisms remain largely unknown. To gain a more extensive understanding of the mode of action of teleost PFOA toxicity, transcriptomics, proteomics, biochemical parameters and reproduction were integrated in the present study. Male and female zebrafish were exposed to nominal concentrations of 0.1; 0.5 and 1 mg/l PFOA for 4 and 28 days resulting in an accumulation which was higher in males compared to females. These gender-related differences were likely caused by different elimination rates due to distinct hormone levels and differences in transport activity by solute carriers. The general mode of action of PFOA was believed to be an increase of the mitochondrial membrane permeability which caused effects on the electron transport system at the biochemical level and resulted in alterations of the oxidative phosphorylation, oxidative stress and apoptosis at the gene transcript and protein level. As a consequence, evidence for the replacement of the affected cells and organelles to sustain tissue homeostasis was found at the molecular level. The higher energy demand, due to these adverse effects, was provided by lowering the glycogen stores. Despite this increase in metabolic expenditure, no effects on reproduction were found indicating that the fish seemed to cope with exposure to the tested concentrations of PFOA.
2013-07-20 | GSE19908 | GEO
Project description:We reported the hepatic gene expression profiling in male Sprague-Dawley rats treated by different concentrations of perfluorooctanoic acid (PFOA) for 7, 14, and 28 days. We confirmed that PFOA induced liver tumor formation was mainly through the activation of peroxisome proliferator-activated receptor α (PPARα). We identified a panel of 7 genes (Cyp4a1, Nr1d1, Acot2, Vnn, Ehhadh, and Acot1) that might serve as the biomarkers for PPARα activation. We also meausred the apical endpoints of PPARα activation and found a good correlation with the expression level of these biomarker genes. Consitituitive androstane receptor mediated Cyp2b enzymatic activity and gene expression was also upregulated by PFOA in a dose-response manner. On the other hand, acyl hydrocarbon receptor (AhR) target gene Cyp1a2 were significantly downregulated at all time points studied. To our surprise, results of KEGG and Reactome pathway analyses suggested that PFOA did not drive the cell cycles and proliferations in the liver. While some of the DNA replication genes such as Pold2 and Mcm8 were upregulated by PFOA treatment, several key cyclin-dependent cell growth genes, including Ccnd1, Ccne2, Ccnb1, and Ccna2 were all significantly downregulated by PFOA in a dose-dependent manner, especailly at 28 days. Ingenuity Pathway Analysis also indicated that PFOA led to a suppression of liver cancer related pathways at later time points studied. These results suggest that while PFOA clearly induced PPARα activation, the increased cell growth (the second key event in the tumor mode of action), was transient and tightly regulated by feedback mechanisms. Whether such changes will eventually cause the formation of preneoplastic foci and liver tumors in rats remains unclear.
2020-01-31 | GSE125762 | GEO
Project description:The aquatic environment is an important site for perfluorooctanoic acid (PFOA) deposit and induced a high risk for aquatic organisms. Nevertheless, the current toxicity assessment was rarely reported the heart effect of PFOA. The exact mode of action and its resulting heterogeneity toxicological effects in aquatic organisms also remain largely unknown. In this study, the heart effects were investigated with a series of assays. The scRNA-seq showed nine cells populations were significantly altered with PFOA exposure. Heart was the mostly influenced cells and the function of cardiac muscle contraction, gas transport and oxygen binding was significantly changed. Moreover, the hatching gland cells, macrophages and lens cells were also significantly influenced with the altered function of apoptosis, endocrine and nervous and immune system. In addition, a significantly decreased swimming behavior and heart morphogenesis were verified.
2022-08-01 | GSE176853 | GEO
Project description:Multiple per- and polyfluoroalkyl substances (PFAS) have been associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver or biologic pathways involved are not known. We performed whole-transcriptome gene expression analysis to investigate the molecular mechanisms of liver toxicity in the dam and female fetuses after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, commonly referred to as GenX).
2022-11-29 | GSE199233 | GEO
Project description:Wistar rats were treated with either PFOA or 8:2 FTOH for 10 days with the following doses, 3, 10 or 25 mg/kg Bwt, followed by one recovery day. The treatment was given daily by i.p. injections. The rats were humanly sacrificed by decapitation, and the liver was immediatly dissected and divided, one piece of the liver was sumerged in RNALater (for use in microarray and realtime experiments) and the other piece of liver was submerged in cold buffer(for ezymatic assays). Pentadecafluorooctanoic (Perfluorooctanoic acid, PFOA) acid is an industrial surfactant. 8:2 FTOH is a fluorotelomer alcohol.
2007-04-10 | E-MEXP-1045 | biostudies-arrayexpress
Project description:Exposure to PFOA during gestation altered the expression of genes related to fatty acid catabolism in both the fetal liver and lung. In the fetal liver, the effects of PFOA were robust and also included genes associated with lipid transport, ketogenesis, glucose metabolism, lipoprotein metabolism, cholesterol biosynthesis, steroid metabolism, bile acid biosynthesis, phospholipid metabolism, retinol metabolism, proteosome activation, and inflammation. These changes are consistent with activation of PPAR alpha. Non-PPAR alpha related changes were suggested as well. Experiment Overall Design: Experiment 1: High Dose: Thirty timed-pregnant CD-1 mice were orally dosed from gestation day 1-17 with either 0, 5, or 10 mg/kg/day PFOA in water. At term, fetal lung and liver were collected, total RNA prepared, and samples pooled from three fetuses per litter. Five biological replicates consisting of individual litter samples were then evaluated for treatment group using Affymetrix mouse 430_2 microarrays. Experiment Overall Design: Experiment 2: Low Dose: Thirty timed-pregnant CD-1 mice were orally dosed from gestation day 1-17 with either 0, 1, or 3 mg/kg/day PFOA in water. At term, fetal lung and liver were collected, total RNA prepared, and samples pooled from three fetuses per litter. Five biological replicates consisting of individual litter samples were then evaluated for treatment group using Affymetrix mouse 430_2 microarrays (note one microarray from the lung + 1mg/kg/day dose group was excluded from the study due to high background). Experiment Overall Design: Please note that each dose experiment had separate concurrent controls.
2008-10-26 | E-GEOD-13044 | biostudies-arrayexpress
Project description:Exposure to PFOA during gestation altered the expression of genes related to fatty acid catabolism in both the fetal liver and lung. In the fetal liver, the effects of PFOA were robust and also included genes associated with lipid transport, ketogenesis, glucose metabolism, lipoprotein metabolism, cholesterol biosynthesis, steroid metabolism, bile acid biosynthesis, phospholipid metabolism, retinol metabolism, proteosome activation, and inflammation. These changes are consistent with activation of PPAR alpha. Non-PPAR alpha related changes were suggested as well. Keywords: gene expression, microarray,PFOA, mouse, fetus, liver
2008-10-07 | GSE13044 | GEO
Project description:Unlike the PPARalpha agonist W14,643, PFOA is capable of inducing effects independently of PPARa. Genes altered in the PPARalpha-null mouse following exposure to PFOA included those associated with fatty acid metabolism, inflammation, xenobiotic metabolism, and cell cycle progression. The specific signaling pathway(s) responsible for these effects is not readily apparent but it is conceivable that other members of the nuclear receptor superfamily such as PPARbeta/delta and CAR may be involved. Keywords: dose response Wild-type and PPARa-null mice were orally dosed for 7 days with either PFOA (1 or 3 mg/kg), the PPARalpha agonist WY-14,643 (50 mg/kg), or compound vehicle. Gene profiling analysis was conducted on 4 animals per group using Applied Biosystems Mouse Genome Survey Microarrays.
2008-05-22 | E-GEOD-9796 | biostudies-arrayexpress
Project description:Modification of gene expression in prostate cancer cells treated with Perfluorooctanoic acid
| PRJNA633102 | ENA