title: Aryl hydrocarbon receptor activation and developmental toxicity in zebrafish in response to soil extracts containing unsubstituted and oxygenated PAHs.
abstract: Many industrial sites are polluted by complex mixtures of polycyclic aromatic compounds (PACs). Besides polycyclic aromatic hydrocarbons (PAHs), these mixtures often contain significant amounts of more polar PACs including oxygenated PAHs (oxy-PAHs). The effects of oxy-PAHs are, however, poorly known. Here we used zebrafish embryos to examine toxicities and transcriptional changes induced by PAC containing soil extracts from three different industrial sites: a gasworks (GAS), a former wood preservation site (WOOD), and a coke oven (COKE), and to PAH and oxy-PAH containing fractions of these. All extracts induced aryl hydrocarbon receptor (Ahr)-regulated mRNAs, malformations, and mortality. The WOOD extract was most toxic and the GAS extract least toxic. The extracts induced glutathione transferases and heat shock protein 70, suggesting that the toxicity also involved oxidative stress. With all extracts, Ahr2-knock-down reduced the toxicity, indicating a significant Ahr2-dependence on the effects. Ahr2-knock-down was most effective with the PAH fraction of the WOOD extract and with the oxy-PAH fraction of the COKE extract. Our results indicate that oxy-PAH containing mixtures can be as potent Ahr activators and developmental toxicants as PAHs. In addition to Ahr activating potency, the profile of cytochrome P4501 inhibitors may also determine the toxic potency of the extracts.
authors.affiliation: †Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.|‡Department of Environmental Toxicology, Uppsala University, 751 05 Uppsala, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Wincent
authors.affiliation: †Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.|‡Department of Environmental Toxicology, Uppsala University, 751 05 Uppsala, Sweden.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Jönsson
authors.affiliation: †Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.affiliation: §Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Lundstedt
authors.affiliation: †Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Kristian
authors.initials: K
authors.lastname: Dreij
mesh_terms: D000818:Animals; D003077:Coke / Q000032:analysis; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007221:Industry; D059206:Natural Gas / Q000032:analysis; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012989:Soil Pollutants / Q000633:toxicity*; D014934:Wood / Q000032:analysis; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*
chemical_list: D003077:Coke; D059206:Natural Gas; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D012989:Soil Pollutants