PCBs : exposures, effects, remediation, and regulation with special emphasis on PCBs in schools

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Environmental Science and Pollution Research 23 (2016): 1971-1974, doi:10.1007/s11356-015-5774-y.The Eighth International PCB Workshop: PCBs in Schools was held in Woods Hole, MA, October 5-9, 2014, and was attended by more than 130 scientists and other interested persons, including citizen’s groups and concerned parents. The program included a wide range of thematic areas. Presentations addressed essential questions and progress toward understanding mechanisms of PCB toxication and risks of PCB exposure. Presentations were also held illuminating several key PCB contamination problems.2016-12-0

Altered gene expression associated with epizootic shell disease in the American lobster, Homarus americanus

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Fish & Shellfish Immunology 29 (2010): 1003-1009, doi:10.1016/j.fsi.2010.08.008.Epizootic shell disease is a poorly understood condition that has significantly affected the American lobster fishery in New England (northeastern US) since the 1990s. Here we present the results of a study to identify changes in gene expression in lobsters exhibiting symptoms of epizootic shell disease. Suppressive subtractive hybridization (SSH) was used to compare gene expression between cDNA pools from diseased (symptomatic) and apparently healthy (asymptomatic) lobsters. Subsequently, quantitative real‐time polymerase chain reaction (qPCR) was used to measure expression of nine genes that were differentially‐expressed in the SSH analysis, in seven tissues (muscle, gill, heart, hepatopancreas, brain, branchiostegite, gonad) dissected from individual symptomatic and asymptomatic lobsters. Expression of arginine kinase (involved in cellular energetics) was significantly decreased in muscle of symptomatic lobsters. Expression of hemocyanin (a respiratory hemolymph protein involved in oxygen transport) was highest in hepatopancreas and showed highly variable expression with a trend toward higher expression in asymptomatic individuals. α2‐Macroglobulin (involved in the innate immune system) was most highly expressed in the ovary, particularly of symptomatic lobsters. The ESTs produced through this study add to the fledgling field of crustacean genomics and revealed three genes that could be further evaluated in lobsters of varying shell disease severity, molt stage, and reproductive condition, for possible implication in epizootic shell disease.Funding for this research was provided by the National Marine Fisheries Service as the ‘New England Lobster Research Initiative: Lobster Shell Disease’ under NOAA grant NA06NMF4720100 to the University of Rhode Island Fisheries Center

Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.) : a CYP3 line in early deuterostomes?

Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular Phylogenetics and Evolution 40 (2006): 760-771, doi:10.1016/j.ympev.2006.04.017.Cytochromes P450 (CYPs) form a gene superfamily involved in the biotransformation of numerous endogenous and exogenous natural and synthetic compounds. In humans, CYP3A4 is regarded as one of the most important CYPs due to its abundance in liver and its capacity to metabolize more than 50% of all clinically used drugs. It has been suggested that all CYP3s arose from a common ancestral gene lineage that diverged between 800 and 1100 million years ago, before the deuterostome-protostome split. While CYP3s are well known in mammals and have been described in lower vertebrates, they have not been reported in non-vertebrate deuterostomes. Members of the genus Ciona belong to the tunicates, whose lineage is thought to be the most basal among the chordates, and from which the vertebrate line diverged. Here we describe the cloning, exon-intron structure, phylogeny, and estimated expression of four novel genes from Ciona intestinalis. We also describe the gene structure and phylogeny of homologous genes in Ciona savignyi. Comparing these genes with other members of the CYP clan 3, show that the Ciona sequences bear remarkable similarity to vertebrate CYP3A genes, and may be an early deuterostome CYP3 line.These studies were supported in part by NIH grant 2-P42-ES07381 to J.J. Stegeman. Tim Verslycke was supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding from the Ocean Life Institute and by a Fellowship of the Belgian American Educational Foundation. Jared Goldstone was supported by a Ruth Kirschstein National Research Service Award (NIH 5F32ES 012794)

Chemical impacts in fish and shellfish from Cape Cod and Massachusetts Bays

This paper is not subject to U.S. copyright. The definitive version was published in Environment Cape Cod 1, no. 3 (1998): 68-85.Mununichogs, soft shell clams, and blue mussels from some or all of 10 sites in Boston Harbor and Massachusetts and Cape Cod Bays were examined histologically: a suite of pathological changes previously known to be associated with chemical contamination were found in animals from the more contaminated sites. In particular, liver tumors were evident in 14% of the adult mununichogs from the Island End River, a tributary of the Mystic River in Boston Harbor. Additionally, a number of pathologies previously shown to be associated with chemical exposure were seen in the two bivalve species at a number of contaminated sites. Induction of cytochrome P45() IA (CYPIA) was also seen in muntntichogs from the more contaminated sites: CYPIA induction is a biochemical change associated with exposure to dioxin and other planar halogenated and aromatic hydrocarbons. These findings suggest that there are measurable biochemical and pathological changes in intertidal fish and shellfish from the more contaminated parts of the Massachusetts Bays system. These types of changes were less evident in the two reference sites in Cape Cod Bay

Cardiovascular gene expression profiles of dioxin exposure in zebrafish embryos

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Society of Toxicology for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 85 (2005): 683-693, doi:10.1093/toxsci/kfi116.2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant that causes altered heart morphology, circulatory impairment, edema, hemorrhage, and early life stage mortality in fish. TCDD toxicity is largely dependent upon the aryl hydrocarbon receptor, but understanding of the molecular mechanism of cardiovascular embryotoxicity remains incomplete. In order to identify genes potentially involved in cardiovascular impacts, we constructed custom cDNA microarrays consisting of 4,896 zebrafish adult heart cDNA clones and over 200 genes with known developmental, toxicological, and housekeeping roles. Gene expression profiles were obtained for 3-day old zebrafish following early embryonic exposure to either 0.5 or 5.0 nM TCDD. 516 clones were significantly differentially expressed (p-value < 0.005) under at least one treatment condition; 123 high-priority clones were selected for further investigation. CYP1A, CYP1B1, and other members of the AHR gene battery, were strongly and dose-dependently induced by TCDD. Importantly, altered expression of cardiac sarcomere components, including cardiac troponin T2 and multiple myosin isoforms, was consistent with the hypothesis that TCDD causes dilated cardiomyopathy. Observed increases in expression levels of mitochondrial energy transfer genes also may be related to cardiomyopathy. Other TCDD-responsive genes included fatty acid and steroid metabolism enzymes, ribosomal and signal transduction proteins, and 18 ESTs with no known protein homologs. As the first broadscale study of TCDD-modulated gene expression in a non-mammalian system, this work provides an important perspective on mechanisms of TCDD toxicity.This work was supported by funding from the National Institutes of Health

Environmental health and the coastal zone

Author Posting. EHP is a publication of the United States government. Publication of EHP lies in the public domain and is therefore without copyright. The definitive version was published in Environmental Health Perspectives 110 (2002): A660-A661.Reconciling coastal development and the maintenance of a quality environment represent an enormous management challenge to both public and private interests. Wise management of coastal areas will require an understanding of the nature of dynamic physical, chemical, and biological interactions in the coastal zone, knowledge of how changes in other components of the Earth system affect coastal zones and their role in global cycles, and insight into how to best use these areas as coastal populations increase. Maintaining the integrity and health of the coastal zone is essential to the quality of marine biological resources and, ultimately, of human life

Nrf2 and Nrf2-related proteins in development and developmental toxicity : insights from studies in zebrafish (Danio rerio)

© The Author(s), 2015. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Free Radical Biology and Medicine 88B (2015): 275-289, doi:10.1016/j.freeradbiomed.2015.06.022.Oxidative stress is an important mechanism of chemical toxicity, contributing to developmental toxicity and teratogenesis as well as to cardiovascular and neurodegenerative diseases and diabetic embryopathy. Developing animals are especially sensitive to effects of chemicals that disrupt the balance of processes generating reactive species and oxidative stress, and those anti-oxidant defenses that protect against oxidative stress. The expression and inducibility of anti-oxidant defenses through activation of NFE2-related factor 2 (Nrf2) and related proteins is an essential process affecting the susceptibility to oxidants, but the complex interactions of Nrf2 in determining embryonic response to oxidants and oxidative stress are only beginning to be understood. The zebrafish (Danio rerio) is an established model in developmental biology and now also in developmental toxicology and redox signaling. Here we review the regulation of genes involved in protection against oxidative stress in developing vertebrates, with a focus on Nrf2 and related cap’n’collar (CNC)-basic-leucine zipper (bZIP) transcription factors. Vertebrate animals including zebrafish share Nfe2, Nrf1, Nrf2, and Nrf3 as well as a core set of genes that respond to oxidative stress, contributing to the value of zebrafish as a model system with which to investigate the mechanisms involved in regulation of redox signaling and the response to oxidative stress during embryolarval development. Moreover, studies in zebrafish have revealed nrf and keap1 gene duplications that provide an opportunity to dissect multiple functions of vertebrate NRF genes, including multiple sensing mechanisms involved in chemical-specific effects.This work was supported in part by National Institutes of Health grants R01ES016366 (MEH), R01ES015912 (JJS), and F32ES017585 (ART-L).2016-06-2

Cytochrome P4501A is induced in endothelial cell lines from the kidney and lung of the bottlenose dolphin, Tursiops truncatus

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 76 (2006): 295-305, doi:10.1016/j.aquatox.2005.10.005.Marine mammals respond to the presence of polycyclic and planar halogenated aromatic hydrocarbons (PAH or PHAH) with the induced expression in endothelium of cytochrome P4501A1, regulated through the aryl hydrocarbon receptor (AHR) transcription factor. Physiological responses in other animals, such as edema and inflammation indicate that the endothelium may be compromised by exposure to AHR agonists, which are ubiquitous in the marine environment. In other mammals and fish the cellular and molecular consequences of exposure to AHR agonists have been elucidated in cultured endothelial cells. We have cultured and characterized cetacean endothelial cells (EC) and used them in induction studies. Endothelial cells were cultured from the lung and kidney of the bottlenose dolphin Tursiops truncatus and exposed to the AHR agonists β-naphthoflavone (βNF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). βNF (1-3 μM) induced significant increases in CYP1A1(O-deethylation of 7-ethoxyresorufin to resorufin;EROD) activity to 3.6 and 0.92 pmol/mg/min in lung and kidney EC, respectively. TCDD was more potent than βNF, and more efficacious, with maximum induction of CYP1A1activity of 10.1 and 15.2 pmol/mg/min in lung and kidney EC at 3-10 nM TCDD. The differential response indicates that the lung and kidney endothelial cells in culture retain the ability to respond in a selective manner to specific stimuli. Both the molecular mechanisms of induction and the physiological consequences, especially in the vasculature, of toxicant exposure can be studied in this system.Part of this work was completed during a faculty fellowship from Fordham University for RAG. The Faculty Research Council of Fordham University provided partial support for RAG. This research was supported by NIH grant 5- P42-ES07381 and by U.S.EPA grant R827102-01-0. This research is an outgrowth and continuing impact of Sea Grant Number Grant No. NA90- AA-D-SG480, project NA86RG0075-R/P61

The new vertebrate CYP1C family : cloning of new subfamily members and phylogenetic analysis

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Biochemical and Biophysical Research Communications 331 (2005): 1016-1024, doi:10.1016/j.bbrc.2005.03.231.Two novel CYP1 genes from teleost fish constituting a new subfamily have been cloned. These paralogous sequences are designated CYP1C1 and CYP1C2. Both genes were initially obtained from untreated scup Stenotomus chrysops tissues by RT-PCR and RACE. Scup CYP1C1 and CYP1C2 code for 524 and 525 amino acids, respectively, and share 80-81% identity at the nucleotide and amino acid levels. Orthologues of CYP1C1 and CYP1C2 were identified in genome databases for other fish species, and both CYP1B1 and CYP1C1 were cloned from zebrafish (Danio rerio). Phylogenetic analysis shows that CYP1Cs and CYP1Bs constitute a sister clade to the CYP1As. Analysis of sequence domains likely to have functional significance suggests the two CYP1Cs in scup may have catalytic functions and/or substrate specificity that differ from each other and from those of mammalian CYP1Bs or CYP1As. RT-PCR results indicate that CYP1C1 and CYP1C2 are variously expressed in several scup organs.This work was supported by EPA grant R 827102-01-0 and NIH grants 5 P42-ES07381 and ES04696. JVG is supported by a Ruth L. Kirschstein NRSA Fellowship (F32 ES012794)