<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mitra Geier</style></author><author><style face="normal" font="default" size="100%">D James Minick</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Susan C Tilton</style></author><author><style face="normal" font="default" size="100%">Pande, Paritosh</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">JG Teeguarden</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Appl Pharmacol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol. Appl. Pharmacol.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Apr 06</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Superfund sites often consist of complex mixtures of polycyclic aromatic hydrocarbons (PAHs). It is widely recognized that PAHs pose risks to human and environmental health, but the risks posed by exposure to PAH mixtures are unclear. We constructed an environmentally relevant PAH mixture with the top 10 most prevalent PAHs (SM10) from a Superfund site derived from environmental passive sampling data. Using the zebrafish model, we measured body burden at 48 hours post fertilization (hpf) and evaluated the developmental and neurotoxicity of SM10 and the 10 individual constituents at 24 hours post fertilization (hpf) and 5 days post fertilization (dpf). Zebrafish embryos were exposed from 6 to 120 hpf to (1) the SM10 mixture, (2) a variety of individual PAHs: pyrene, fluoranthene, retene, benzo[a]anthracene, chrysene, naphthalene, acenaphthene, phenanthrene, fluorene, and 2-methylnaphthalene. We demonstrated that SM10 and only 3 of the individual PAHs were developmentally toxic. Subsequently, we constructed and exposed developing zebrafish to two sub-mixtures: SM3 (comprised of 3 of the developmentally toxicity PAHs) and SM7 (7 non-developmentally toxic PAHs). We found that the SM3 toxicity profile was similar to SM10, and SM7 unexpectedly elicited developmental toxicity unlike that seen with its individual components. The results demonstrated that the overall developmental toxicity in the mixtures could be explained using the general concentration addition model. To determine if exposures activated the AHR pathway, spatial expression of CYP1A was evaluated in the 10 individual PAHs and the 3 mixtures at 5 dpf. Results showed activation of AHR in the liver and vasculature for the mixtures and some individual PAHs. Embryos exposed to SM10 during development and raised in chemical-free water into adulthood exhibited decreased learning and responses to startle stimulus indicating that developmental SM10 exposures affect neurobehavior. Collectively, these results exemplify the utility of zebrafish to investigate the developmental and neurotoxicity of complex mixtures.&lt;/p&gt;
</style></abstract></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Goodale, Britton C</style></author><author><style face="normal" font="default" size="100%">Susan C Tilton</style></author><author><style face="normal" font="default" size="100%">Corvi, Margaret M</style></author><author><style face="normal" font="default" size="100%">Glenn R Wilson</style></author><author><style face="normal" font="default" size="100%">Janszen, Derek B</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Katrina M Waters</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Appl Pharmacol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol. Appl. Pharmacol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Embryo, Nonmammalian</style></keyword><keyword><style  face="normal" font="default" size="100%">Polycyclic Hydrocarbons, Aromatic</style></keyword><keyword><style  face="normal" font="default" size="100%">Structure-Activity Relationship</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Zebrafish</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">11/2013</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">272</style></volume><pages><style face="normal" font="default" size="100%">656-70</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the aryl hydrocarbon receptor (AHR) in a structurally dependent manner, and induce toxicity via both AHR-dependent and -independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at concentrations that induced developmental malformations by 120 h post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burdens were analyzed at both time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the least number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure, and may provide a path for unraveling the toxicity of complex PAH mixtures.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/23656968?dopt=Abstract</style></custom1></record></records></xml>