TitleComparative developmental toxicity of environmentally relevant oxygenated PAHs.
Publication TypeJournal Article
AuthorsKnecht AL, Goodale BC, Truong L, Simonich MT, Swanson AJ, Matzke MM, Anderson KA, Waters KM, Tanguay RL
JournalToxicol Appl Pharmacol
Date Published11/2013
Abnormalities, Drug-Induced, Animals, Biological Markers, Embryo, Nonmammalian, Environmental Pollutants, Extracellular Space, Gene Expression Regulation, Developmental, Immunohistochemistry, Mitochondria, Oxidation-Reduction, Oxidative Stress, Oxygen Consumption, Polycyclic Hydrocarbons, Aromatic, Real-Time Polymerase Chain Reaction, RNA, Teratogens, Zebrafish

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.

Alternate JournalToxicol. Appl. Pharmacol.
PubMed ID23684558
PubMed Central IDPMC3976560
Grant ListF31 ES019445 / ES / NIEHS NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
RC4 ES019764 / ES / NIEHS NIH HHS / United States
RC4ES019764 / ES / NIEHS NIH HHS / United States
T32 ES007060 / ES / NIEHS NIH HHS / United States
T32ES7060 / ES / NIEHS NIH HHS / United States