Comparative developmental toxicity of environmentally relevant oxygenated PAHs

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 120 h 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 48 hpf, 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 26 hpf 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.

Global long-range transport and lung cancer risk from polycyclic aromatic hydrocarbons shielded by coatings of organic aerosol

“…However, recent experimental studies show that several oxidized PAHs could remain particle-bound, and often appear as higher molecular weight peaks in particle mass spectra (25,39). Some oxidized BaP species have been shown to be toxic (40), and some are direct-acting mutagens (39); therefore, it is important to quantify their atmospheric exposure. Here, we track the oxidation Global and regional population-weighted ILCR for PAH mixtures calculated for the default unshielded (red) and new shielded (blue) modeling formulations using 0.1°× 0.1°downscaled BaP concentrations, as described in SI Appendix.…”

Occurrence and Potential Sources of Quinones Associated with PM2.5 in Guadalajara, Mexico

“…In addition to direct mutagenicity and carcinogenicity [4,5], in vivo assays have shown that quinones are highly redox active, cascading the formation of reactive oxygen species (ROS) within the cell [6]. The presence of ROS can cause severe oxidative stress within cells [7] and lead to the development of diseases and pathological conditions such as asthma, cardiovascular diseases, Alzheimer, diabetes, or cancer [8].…”

Effect of dispersed crude oil on cardiac function in seabass Dicentrarchus labrax

“…Studies have shown that after contamination, PAHs are preferentially localized in the mitochondria (Zhu et al, 1995). Moreover, a decrease in mitochondrial O 2 consumption rate has been observed in zebrafish after exposure to a cocktail of PAHs (Knecht et al, 2013). In this study, the permeabilization of cells using saponin made possible to analyze functional mitochondria in situ, in their normal intracellular position, and the use of selected substrates and inhibitors allowed the analysis of different elements of the respiratory chain.…”

“…In fact, these highly reactive products are known to have a negative impact on complexes I, III and IV of the respiratory chain (Musatov and Robinson, 2012). If, petroleum compounds are known to induce mitochondrial alteration (Zhu et al, 1995;Knecht et al, 2013), dispersants could also have the same mechanism of action. They appear to stimulate ROS production: a study of Milinkovitch et al (2013) has shown increased antioxidant defenses in the hearts of Liza aurata exposed to Finasol OSR 62.…”