%0 Journal Article %J Toxicol Appl Pharmacol %D 2013 %T Comparative developmental toxicity of environmentally relevant oxygenated PAHs. %A Knecht, Andrea L %A Goodale, Britton C %A Truong, Lisa %A Simonich, Michael T %A Swanson, Annika J %A Matzke, Melissa M %A Kim A Anderson %A Katrina M Waters %A Robyn L Tanguay %K Abnormalities, Drug-Induced %K Animals %K Biological Markers %K Embryo, Nonmammalian %K Environmental Pollutants %K Extracellular Space %K Gene Expression Regulation, Developmental %K Immunohistochemistry %K Mitochondria %K Oxidation-Reduction %K Oxidative Stress %K Oxygen Consumption %K Polycyclic Hydrocarbons, Aromatic %K Real-Time Polymerase Chain Reaction %K RNA %K Teratogens %K Zebrafish %X

Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are byproducts of combustion and photo-oxidation of parent PAHs. OPAHs are widely present in the environment and pose an unknown hazard to human health. The developing zebrafish was used to evaluate a structurally diverse set of 38 OPAHs for malformation induction, gene expression changes and mitochondrial function. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to a dilution series of 38 different OPAHs and evaluated for 22 developmental endpoints. AHR activation was determined via CYP1A immunohistochemistry. Phenanthrenequinone (9,10-PHEQ), 1,9-benz-10-anthrone (BEZO), xanthone (XAN), benz(a)anthracene-7,12-dione (7,12-B[a]AQ), and 9,10-anthraquinone (9,10-ANTQ) were evaluated for transcriptional responses at 48hpf, prior to the onset of malformations. qRT-PCR was conducted for a number of oxidative stress genes, including the glutathione transferase(gst), glutathione peroxidase(gpx), and superoxide dismutase(sod) families. Bioenergetics was assayed to measure in vivo oxidative stress and mitochondrial function in 26hpf embryos exposed to OPAHs. Hierarchical clustering of the structure-activity outcomes indicated that the most toxic of the OPAHs contained adjacent diones on 6-carbon moieties or terminal, para-diones on multi-ring structures. 5-carbon moieties with adjacent diones were among the least toxic OPAHs while the toxicity of multi-ring structures with more centralized para-diones varied considerably. 9,10-PHEQ, BEZO, 7,12-B[a]AQ, and XAN exposures increased expression of several oxidative stress related genes and decreased oxygen consumption rate (OCR), a measurement of mitochondrial respiration. Comprehensive in vivo characterization of 38 structurally diverse OPAHs indicated differential AHR dependency and a prominent role for oxidative stress in the toxicity mechanisms.

%B Toxicol Appl Pharmacol %V 271 %P 266-75 %8 11/2013 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/23684558?dopt=Abstract %R 10.1016/j.taap.2013.05.006 %0 Journal Article %J Toxicology %D 2012 %T Neurodevelopmental low-dose bisphenol A exposure leads to early life-stage hyperactivity and learning deficits in adult zebrafish. %A Saili, Katerine S %A Corvi, Margaret M %A Weber, Daniel N %A Patel, Ami U %A Das, Siba R %A Przybyla, Jennifer %A Kim A Anderson %A Robyn L Tanguay %K Animals %K Behavior, Animal %K Benzhydryl Compounds %K Chromatography, High Pressure Liquid %K Dose-Response Relationship, Drug %K Embryo, Nonmammalian %K Endocrine Disruptors %K Environmental Pollutants %K Estradiol %K Hydrazines %K Hyperkinesis %K Larva %K Learning Disorders %K Maze Learning %K Phenols %K Receptors, Estrogen %K Receptors, G-Protein-Coupled %K Reversal Learning %K Teratogens %K Zebrafish %X

Developmental bisphenol A (BPA) exposure has been implicated in adverse behavior and learning deficits. The mode of action underlying these effects is unclear. The objectives of this study were to identify whether low-dose, developmental BPA exposure affects larval zebrafish locomotor behavior and whether learning deficits occur in adults exposed during development. Two control compounds, 17β-estradiol (an estrogen receptor ligand) and GSK4716 (a synthetic estrogen-related receptor gamma ligand), were included. Larval toxicity assays were used to determine appropriate BPA, 17β-estradiol, and GSK4716 concentrations for behavior testing. BPA tissue uptake was analyzed using HPLC and lower doses were extrapolated using a linear regression analysis. Larval behavior tests were conducted using a ViewPoint Zebrabox. Adult learning tests were conducted using a custom-built T-maze. BPA exposure to <30μM was non-teratogenic. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1μM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1μM 17β-estradiol or GSK4716 also led to larval hyperactivity. This study demonstrates the efficacy of using the zebrafish model for studying the neurobehavioral effects of low-dose developmental BPA exposure.

%B Toxicology %V 291 %P 83-92 %8 01/2012 %G eng %N 1-3 %1 http://www.ncbi.nlm.nih.gov/pubmed/22108044?dopt=Abstract %R 10.1016/j.tox.2011.11.001