Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Human fetal penile smooth muscle cells (hfPSCM): Control vs PCB mixtures treatments

ABSTRACT: The effects exerted by three mixtures of Polychlorinated Biphenyls (PCB), one featuring dioxin-like (DL) and two featuring non dioxin-like (NDL) congeners, on human fetal corpora cavernosa cells representative of a major male endocrine-sensitive organ, have been evaluated by gene expression profiling. PCB congeners concentrations used were derived from human internal exposure data to explore the impact of the adult body burden on a fetal tissue. Cell exposure were performed for 72h mimicking a chronic exposure. Experiment conditions: control, three treatments with PCB-Mix1, PCB-Mix2 or PCB-Mix3. Biological replicates: 3 control replicates, 3 replicates per treatment. Technical replica: 2 (dye swap) per biological replica. Direct comparison design (control vs treated samples) in 12/16 arrays (biological replicates 1 and 2); Loop design in 4/16 arrays (biological replicate 3).

ORGANISM(S): Homo sapiens

SUBMITTER: Sabrina Tait

PROVIDER: E-GEOD-25193 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:(Abstract) Toxicogenomics has great potential for enhancing our understanding of environmental chemical toxicity, hopefully leading to better-informed human health risk assessments. This study employed toxicogenomic technology to reveal species differences in response to two prototypical aryl hydrocarbon receptor (AHR) agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the polychlorinated biphenyl (PCB) congener PCB 126. Dose responses of primary cultures of rat and human hepatocytes were determined using species-specific microarrays sharing over 4,000 gene orthologs. Forty-seven human and 79 rat genes satisfied dose response criteria for both chemicals and were subjected to further analysis including the calculation of EC50 and the relative potency (REP) of PCB 126 for each gene. Only 5 responsive orthologous genes were shared between the two species, yet the geometric mean of the REPs for all rat and human modeled responsive genes were 0.06 (95% Confidence Interval (CI); 0.03-0.1) and 0.002 (95% CI; 0.001-0.005), respectively, suggesting broad species differences in the initial events that follow AHR activation but precede toxicity. This indicates that there are species differences in both the specific genes that responded and the agonist potency and relative potency for those genes. This observed insensitivity of human cells to PCB 126 is consistent with more traditional measurements of AHR activation (i.e., CYP1A1 enzyme activity) and suggests that the species difference in PCB 126 sensitivity is likely due to certain aspects of AHR function. That a species divergence also exists in this expanded AHR-regulated gene repertoire is a novel finding and should help when extrapolating animal data to humans. Experiment Overall Design: Primary hepatocyte cultures, separated into 2 pools of 3 female Sprague Dawley rats each, were treated with vehicle (0.5% DMSO), TCDD (-14 to -6.5 log10 M) , or PCB 126 (-12 to -5 log10 M) for 48h. Total RNA was extracted and screened with RG-U34A microarrays for dose response.

Project description:(Abstract) Toxicogenomics has great potential for enhancing our understanding of environmental chemical toxicity, hopefully leading to better-informed human health risk assessments. This study employed toxicogenomic technology to reveal species differences in response to two prototypical aryl hydrocarbon receptor (AHR) agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the polychlorinated biphenyl (PCB) congener PCB 126. Dose responses of primary cultures of rat and human hepatocytes were determined using species-specific microarrays sharing over 4,000 gene orthologs. Forty-seven human and 79 rat genes satisfied dose response criteria for both chemicals and were subjected to further analysis including the calculation of EC50 and the relative potency (REP) of PCB 126 for each gene. Only 5 responsive orthologous genes were shared between the two species, yet the geometric mean of the REPs for all rat and human modeled responsive genes were 0.06 (95% Confidence Interval (CI); 0.03-0.1) and 0.002 (95% CI; 0.001-0.005), respectively, suggesting broad species differences in the initial events that follow AHR activation but precede toxicity. This indicates that there are species differences in both the specific genes that responded and the agonist potency and relative potency for those genes. This observed insensitivity of human cells to PCB 126 is consistent with more traditional measurements of AHR activation (i.e., CYP1A1 enzyme activity) and suggests that the species difference in PCB 126 sensitivity is likely due to certain aspects of AHR function. That a species divergence also exists in this expanded AHR-regulated gene repertoire is a novel finding and should help when extrapolating animal data to humans. Experiment Overall Design: Primary hepatocyte cultures derived from 3 human donors were treated with vehicle (0.5% DMSO), TCDD (-14 to -6.5 log10 M) , or PCB 126 (-12 to -5 log10 M) for 48h. Total RNA was extracted and screened with HG-U133A microarrays for dose response.

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Human fetal penile smooth muscle cells (hfPSCM): Control vs PCB mixtures treatments

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