Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: Dose-dependent changes in the RLWs 24 h post dose for TCDD, PCB126, and TCDF. Results are displayed as mean ± SE of at least four independent replicates. Data were analyzed by ANOVA followed by Dunnett’s post hoc test: *p < 0.05 for vehicle versus treated samples. No additional significant treatment-related alterations in liver or organ weights were noted in the dose-response study.

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques:

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: Hepatic (A) TCDD, (B) PCB126, and (C) TCDF levels per g liver wet weight measured 24 h post dose using HRGC/HRMS. The data are displayed on a log scale to visualize tissue concentrations at all doses. The results are displayed as mean ± SE of at least three independent samples. Data were analyzed by ANOVA followed by Dunnett’s post hoc test: *p< 0.05 for vehicle versus treated samples.

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques:

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: Absolute Hepatic Tissue Levels (in pg/g or ppt per wet weight) for TCDD-, PCB126-, and TCDF-Treated Samples and Vehicle Controls Measured by HRGC/HRMS

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques:

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: Dose-Dependent Incidence and Severity of Hepatic Histopathological Responses in the Vehicle, TCDD-, PCB126-, and TCDF-Treated Mice at 24 h

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques:

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: Representative hematoxylin and eosin–stained liver sections 224 h postexposure to PCB126, TCDF, or TCDD. Selected doses resulted in vacuolization, single cell necrosis, and/or immune cell infiltration. (A) Vehicle treatment resulted in no visible hepatic alterations. (B) 300 μg/kg PCB126 elicited minimal vacuolization compared with (C) 1000 μg/kg TCDF and (D) 300 μg/kg TCDD, which exhibited more pronounced vacuolization. (E) 3000 μg/kg TCDF resulted in immune cell infiltration as well as (F) instances of necrosis (arrow). Bars = 50 μm.

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques: Staining

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: Dose-dependent induction of EROD activity following exposure to TEF-equivalent doses of TCDD, PCB126, and TCDF. The ToxResponse Modeler calculated ED50 values of 1.1, 53.6, and 54.2 μg/kg for TCDD, PCB126, and TCDF, respectively, yielding PCB126 and TCDF EROD REPs of 0.02. Symbols represent the mean ± SE of four independent samples. Sigmoidal dose-response curve fitting was done using GraphPad Prism 5.0.

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques: Activity Assay

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: (A) Comprehensive TCDD, TCDF, and PCB126 dose-response analysis—Part 1/3. Differentially regulated features were identified using a relaxed P1(t) cutoff of 0.90 to maximize the number of differentially expressed genes under consideration. TCDD elicited ∼1.6 times more differentially expressed features compared with TCDF (13,476 vs. 8655) and ∼1.3 times more differentially expressed features compared with PCB126 (13,476 vs. 10,983). Unions were taken to identify all differentially regulated features. Features missing data at any dose, as well as Agilent controls, were removed and not considered further. Features were mapped to specific genes for further analysis. (B) Comprehensive TCDD, TCDF, and PCB126 dose-response analysis—Part 2/3. Differentially expressed genes were analyzed further if the change in expression was greater than 1.5-fold for at least one dose. Genes exhibiting a sigmoidal dose-response were identified and intersected to identify genes responsive to both TCDD and TCDF and to TCDD and PCB126 at 24 h. Genes were examined further if the model-based ED50 value, calculated by ToxResponse Modeler, was within the experimental dose range. Genes exhibiting a sigmoidal dose-response curve for both TCDD and TCDF were intersected to identify 1506 genes that exhibited an expression change greater than 1.5-fold for at least one dose, a P1(t) > 0.90, a sigmoidal profile, and an ED50 value within the experimental range. Identical analysis yielded only 388 sigmoidal genes for TCDD and PCB126. PCB126 lost a majority of differentially expressed dose-responsive genes from further consideration because the ED50s were not within the experimental dose range. (C) Comprehensive TCDD, TCDF, and PCB126 dose-response analysis—Part 3/3. In the final analysis, assumptions regarding similarities in the slopes and shapes of corresponding TCDD and TCDF as well as TCDD and PCB126 sigmoidal dose-response curves were assessed by calculating the correlation coefficients of the elicited dose-response curves. The correlation analysis identified 210 genes from TCDD versus TCDF comparisons, and only 40 genes from TCDD and PCB126 comparisons with correlation coefficients greater than 0.60. The distribution of individual gene expression REPs is provided. The median REP for hepatic gene expression in the immature ovariectomized C57BL/6 mouse at 24 h was calculated to be 0.06 and 0.02 for TCDF and PCB126, respectively.

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques: Expressing, Gene Expression

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: Three-way Venn analysis of TCDD, PCB126, and TCDF elicited differentially expressed genes at (A) stringent (|fold change| > 1.5, P1(t) > 0.99) and (B) relaxed statistical criteria (|fold change| > 1.5, P1(t) > 0.90).

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques:

Journal: Toxicological Sciences

Article Title: Automated Dose-Response Analysis and Comparative Toxicogenomic Evaluation of the Hepatic Effects Elicited by TCDD, TCDF, and PCB126 in C57BL/6 Mice

doi: 10.1093/toxsci/kfq236

Figure Lengend Snippet: QRT-PCR verification of selected AhR-regulated genes: Cyp1a1, Cyp1a2, Nqo1, Tiparp, and Notch1 for (A) TCDD, (B) PCB126, and (C) TCDF at 24 h. The same RNA samples used in the dose-response microarray studies were also used for QRT-PCR analysis. All fold changes were calculated relative to vehicle controls. Bars (left y-axis) and lines (right y-axis) represent QRT-PCR and microarray data, respectively. The genes are represented by their official gene symbols. Bars represent the mean ± SE of four independent QRT-PCR samples. QRT-PCR data were analyzed by ANOVA followed by Dunnett’s post hoc test: *p < 0.05 for vehicle versus treated samples. ED50 values for microarray and QRT-PCR mRNA levels are provided in Supplementary table 7.

Article Snippet: TCDD and TCDF were gifts from The Dow Chemical Company (Midland, MI).

Techniques: Quantitative RT-PCR, Microarray

Journal: Gut Microbes

Article Title: Metabolic impact of persistent organic pollutants on gut microbiota

doi: 10.1080/19490976.2020.1848209

Figure Lengend Snippet: Pathway enrichment analysis of metatranscriptomic data

Article Snippet: POPs including TCDD, TCDF, PCB-126, and PCB-153 ( )) were purchased from Cambridge Isotope Laboratories, Inc. (Tewksbury, MA) and suspended in dimethyl sulfoxide (Sigma-Aldrich, St. Louis, MO).

Techniques: Chemotaxis Assay, Homologous Recombination, Starch