Top Papers in Environmental Science, Second Runner-Up (Tie): Uncoupled frozen fish
JULIETTE LEGLER, VU UNIVERSITY
sion of hundreds of genes. “You get bromodiphenylether (BDE-47)sinto “Microarray Analysis Reveals a so much information and data, if 6-hydroxy-BDE-47. But virtually Mechanism of Phenolic Polybromiyou look at it gene by gene, you nothing is known about its toxicity. nated Diphenylether Toxicity in Zewon’t be able to figure out what the “Frozen fish” got Legler hooked brafish” by Antonius L. van Boxtel, compound does,” he explains. on the project about 5 years ago. Jorke H. Kamstra, Peter H. Cenijn, The breakthrough came when When she exposed zebrafish eggs Abraham Brouwer, Klaas Krab, Julitoxicologist Bram Brouwer ette Legler, and Marijke J. remarked that the “frozen Wagner, VU University, Amfish” phenomenon looked sterdam; Bart Pieterse and like disruption of oxidative Bart van der Burg, BioDetecphosphorylation, a metabolic tion Systems BV, Amsterpathway shared by all living dam; Maartje Antink, Service things that converts carbohyXS BV, Leiden (The Netherdrates to energy. Then van lands); and Go¨ran Marsh, Boxtel, together with Bart Stockholm University, 2008, Pieterse, a bioinformatics 42 (5), 1773-1779; DOI expert with BioDetection 10.1021/es0720863. Systems BV in Amsterdam, It all started when enviexamined them in clusters ronmental toxicologist Juliinstead of looking at indiette Legler enticed Antonius vidual genes and uncovered “Thijs” van Boxtel to leave a pattern: the metabolite was sunny Australia to pursue a disrupting a specific group of Ph.D. in her lab at VU Uni- Antonius van Boxtel’s research on PBDEs brought technoloproteins involved in a proton versity in Amsterdam. After gies from molecular biology into the field of toxicology, earning a master’s degree in which was something the scientist says he had longed to do. transport step in oxidative phosphorylation. molecular biology at Utrecht to 6-hydroxy-BDE-47, development Unlike most researchers who University (The Netherlands), van froze to a halt 19-20 hours after stop after the microarray fingers Boxtel had joined Paul Vermer’s lab fertilization. Adult fish exposed to affected genes, Legler’s team took in Melbourne where he was working the metabolite behaved as though the next step and proved its hyon generating stem cells from ordithey were suffocating. pothesis by measuring changes in nary somatic cells from mouse Previous research had shown respiration and membrane potentissue. that the metabolite was an endotial in rat mitochondria. On a visit to Australia, Legler told crine disrupter. “But the fish died “If oxidative phosphorylation is van Boxtel about an emerging so quickly that the hormone pathdisrupted, organisms can’t get project that was to lead to an ES&T ways could not be that important, enough energy, and they waste best paper of 2008. She encouraged and it gave us an idea that someaway,” Legler says. van Boxtel to examine the toxicity of thing was wrong in a fundamental “This opens up new areas of rea common metabolite of brominated process,” Legler says. search,” van Boxtel says. Other meflame retardants and uncover the The quest for answers got a tabolites of PBDEs also uncouple molecular mechanism for its acute boost from a European project oxidative phosphorylation, as do called FIRE, the Flame Retardants effects on zebrafish. The project ubiquitous contaminants such as Integrated Risk Assessment for Enwould push the envelope of conhydroxylated PCBs and perfluoridocrine Effects, Legler says. Chemtaminant research by bringing technated compounds, he says. Scienist Åke Bergman at Stockholm nologies from molecular biology into tists now are finding emaciated fish University, a FIRE member, synthethe field of toxicology, something in Europe and emaciated seals in sized the PBDE metabolites and van Boxtel had been longing to do. “I the Baltic Sea, possibly because supplied Legler’s team. had a feeling it would lead to somemany pollutants uncouple oxidaWhen van Boxtel came on board, thing big,” he says. tive phosphorylation and accumuhe analyzed a fish cell line that was The flame retardants known as late in animals, he adds. exposed to the compound with a PBDEs are rapidly accumulating in —JANET PELLEY microarraysa chip that can detect the environment and in fish and huchanges in the expression of genes. mans. Animals metabolize one of the The metabolite altered the expresmost common PBDEss2,2′,4,4′-tetra2200 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / April 1, 2009
10.1021/es900350z
2009 American Chemical Society
Published on Web 02/18/2009
