title: A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant.
abstract: The Deepwater Horizon disaster drew global attention to the toxicity of crude oil and the potential for adverse health effects amongst marine life and spill responders in the northern Gulf of Mexico. The blowout released complex mixtures of polycyclic aromatic hydrocarbons (PAHs) into critical pelagic spawning habitats for tunas, billfishes, and other ecologically important top predators. Crude oil disrupts cardiac function and has been associated with heart malformations in developing fish. However, the precise identity of cardiotoxic PAHs, and the mechanisms underlying contractile dysfunction are not known. Here we show that phenanthrene, a PAH with a benzene 3-ring structure, is the key moiety disrupting the physiology of heart muscle cells. Phenanthrene is a ubiquitous pollutant in water and air, and the cellular targets for this compound are highly conserved across vertebrates. Our findings therefore suggest that phenanthrene may be a major worldwide cause of vertebrate cardiac dysfunction.
authors.affiliation: Stanford University, Biology Department, Hopkins Marine Station, Pacific Grove, CA, 93950, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Brette
authors.affiliation: Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9NT, UK.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Shiels
authors.affiliation: Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9NT, UK.
authors.forename: Gina L J
authors.initials: GL
authors.lastname: Galli
authors.affiliation: Stanford University, Biology Department, Hopkins Marine Station, Pacific Grove, CA, 93950, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cros
authors.affiliation: National Oceanic and Atmospheric Administration, Northwest Fisheries Science Center, Seattle, Washington, 98112, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Incardona
authors.affiliation: National Oceanic and Atmospheric Administration, Northwest Fisheries Science Center, Seattle, Washington, 98112, USA.
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Scholz
authors.affiliation: Stanford University, Biology Department, Hopkins Marine Station, Pacific Grove, CA, 93950, USA.|Tuna Research and Conservation Center, Stanford University Hopkins Marine Station, Pacific Grove, CA, 93950, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Block
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005399:Fishes; D006352:Heart Ventricles / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010616:Phenanthrenes / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D010616:Phenanthrenes; D011084:Polycyclic Aromatic Hydrocarbons; D014874:Water Pollutants, Chemical; C031181:phenanthrene; D002118:Calcium