%0 Audiovisual Material %D 2023 %T Comparative Hazard Potential of Environmentally Relevant Alkylated Polycyclic Aromatic Hydrocarbons %A M. L. Morshead %A Truong, Lisa %A Simonich, Michael T %A J. Scotten %A Kim A Anderson %A Robyn L Tanguay %B Society of Toxicology 62nd Annual Meeting in Nashville, TN %8 03/2023 %G eng %0 Journal Article %J Arch Toxicol %D 2018 %T Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons. %A Mitra Geier %A Chlebowski, Anna C %A Truong, Lisa %A Staci M Simonich %A Kim A Anderson %A Robyn L Tanguay %K Animals %K Cytochrome P-450 CYP1A1 %K Embryo, Nonmammalian %K Larva %K Polycyclic Aromatic Hydrocarbons %K Toxicity Tests %K Zebrafish %X

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that occur in complex mixtures. Several PAHs are known or suspected mutagens and/or carcinogens, but developmental toxicity data is lacking for PAHs, particularly their oxygenated and nitrated derivatives. Such data are necessary to understand and predict the toxicity of environmental mixtures. 123 PAHs were assessed for morphological and neurobehavioral effects for a range of concentrations between 0.1 and 50 µM, using a high throughput early-life stage zebrafish assay, including 33 parent, 22 nitrated, 17 oxygenated, 19 hydroxylated, 14 methylated, 16 heterocyclic, and 2 aminated PAHs. Additionally, each PAH was evaluated for AHR activation, by assessing CYP1A protein expression using whole animal immunohistochemistry (IHC). Responses to PAHs varied in a structurally dependent manner. High-molecular weight PAHs were significantly more developmentally toxic than the low-molecular weight PAHs, and CYP1A expression was detected in five distinct tissues, including vasculature, liver, skin, neuromasts and yolk.

%B Arch Toxicol %V 92 %P 571-586 %8 2018 Feb %G eng %N 2 %R 10.1007/s00204-017-2068-9 %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