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Comparative developmental toxicity of environmentally relevant oxygenated PAHs.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2013 Sep 01; Vol. 271 (2), pp. 266-75. Date of Electronic Publication: 2013 May 14. - Publication Year :
- 2013
-
Abstract
- 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.<br /> (Published by Elsevier Inc.)
- Subjects :
- Abnormalities, Drug-Induced pathology
Animals
Biomarkers metabolism
Embryo, Nonmammalian
Extracellular Space metabolism
Gene Expression Regulation, Developmental drug effects
Immunohistochemistry
Mitochondria metabolism
Oxidation-Reduction
Oxidative Stress drug effects
Oxygen Consumption physiology
RNA biosynthesis
RNA genetics
Real-Time Polymerase Chain Reaction
Environmental Pollutants toxicity
Polycyclic Aromatic Hydrocarbons toxicity
Teratogens
Zebrafish physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 271
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 23684558
- Full Text :
- https://doi.org/10.1016/j.taap.2013.05.006