Biomedical subjects

Tracy K Collier

Publications and source records attributed to Tracy K Collier.

6 recordsLinked to original sources

PubMed2006

Developmental toxicity of 4-ring polycyclic aromatic hydrocarbons in zebrafish is differentially dependent on AH receptor isoforms and hepatic cytochrome P4501A metabolism.

Polycyclic aromatic hydrocarbons (PAHs) derived from fossil fuels are ubiquitous contaminants and occur in aquatic habitats as highly variable and complex mixtures of compounds containing 2 to 6 rings. For aquatic species, PAHs are generally accepted as acting through either of two modes of action: (1) "dioxin-like" toxicity mediated by activation of the aryl hydrocarbon receptor (AHR), which controls a battery of genes involved in PAH metabolism, such as cytochrome P4501A (CYP1A) and (2) "nonpolar narcosis", in which tissue uptake is dependent solely on hydrophobicity and toxicity is mediated through non-specific partitioning into lipid bilayers. As part of a systematic analysis of mechanisms of PAH developmental toxicity in zebrafish, we show here that three tetracyclic PAHs (pyrene, chrysene, and benz[a]anthracene) activate the AHR pathway tissue-specifically to induce distinct patterns of CYP1A expression. Using morpholino knockdown of ahr1a, ahr2, and cyp1a, we show that distinct embryolarval syndromes induced by exposure to two of these compounds are differentially dependent on tissue-specific activation of AHR isoforms or metabolism by CYP1A. Exposure of embryos with and without circulation (silent heart morphants) resulted in dramatically different patterns of CYP1A induction, with circulation required to deliver some compounds to internal tissues. Therefore, biological effects of PAHs cannot be predicted simply by quantitative measures of AHR activity or a compound's hydrophobicity. These results indicate that current models of PAH toxicity in fish are greatly oversimplified and that individual PAHs are pharmacologically active compounds with distinct and specific cellular targets.

Abnormalities, Drug-Induced↗

PubMed2006

Contaminant exposure in outmigrant juvenile salmon from Pacific Northwest estuaries of the United States.

To better understand the dynamics of contaminant uptake in outmigrant juvenile salmon in the Pacific Northwest, concentrations of polychlorinated biphenyls (PCBs), DDTs, polycylic aromatic hydrocarbons (PAHs) and organochlorine pesticides were measured in tissues and prey of juvenile chinook and coho salmon from several estuaries and hatcheries in the US Pacific Northwest. PCBs, DDTs, and PAHs were found in tissues (whole bodies or bile) and stomach contents of chinook and coho salmon sampled from all estuaries, as well as in chinook salmon from hatcheries. Organochlorine pesticides were detected less frequently. Of the two species sampled, chinook salmon had the highest whole body contaminant concentrations, typically 2--5 times higher than coho salmon from the same sites. In comparison to estuarine chinook salmon, body burdens of PCBs and DDTs in hatchery chinook were relatively high, in part because of the high lipid content of the hatchery fish. Concentrations of PCBs were highest in chinook salmon from the Duwamish Estuary, the Columbia River and Yaquina Bay, exceeding the NOAA Fisheries' estimated threshold for adverse health effects of 2400 ng/g lipid. Concentrations of DDTs were especially high in juvenile chinook salmon from the Columbia River and Nisqually Estuary; concentrations of PAH metabolites in bile were highest in chinook salmon from the Duwamish Estuary and Grays Harbor. Juvenile chinook salmon are likely absorbing some contaminants during estuarine residence through their prey, as PCBs, PAHs, and DDTs were consistently present in stomach contents, at concentrations significantly correlated with contaminant body burdens in fish from the same sites.

Animals↗

PubMed2006

Dose-additive inhibition of chinook salmon acetylcholinesterase activity by mixtures of organophosphate and carbamate insecticides.

Organophosphate and carbamate insecticides are widely detected in surface waters of the western United States. These chemicals interfere with acetylcholine-mediated synaptic transmission in the nervous systems of fish and other aquatic animals via the inhibition of AChE (acetylcholinesterase) enzyme activity. Anticholinesterase insecticides commonly co-occur in the environment. This raises the possibility of antagonistic, additive, or synergistic neurotoxicity in exposed fish, including threatened and endangered species of Pacific salmon. We extracted AChE from the olfactory nervous system of chinook salmon (Oncorhynchus tshawytscha) and investigated the inhibitory effects of organophosphates (the oxon derivatives of diazinon, chlorpyrifos, and malathion) and carbamates (carbaryl and carbofuran), alone and in two-way combinations. We found that the joint toxicity of anticholinesterase mixtures can be accurately predicted from the inhibitory potencies of individual chemicals within a mixture. This indicates that organophosphate and carbamate insecticides are noninteractive in terms of AChE inhibition and that it might be possible to estimate the cumulative neurotoxicity of mixtures by simple dose addition. Because organophosphates and carbamates are likely to have additive effects on the neurobehavior of salmon under natural exposure conditions, ecological risk assessments that focus on individual anticholinesterases might underestimate the actual risk to salmon in watersheds in which mixtures of these chemicals occur.

Acetylcholinesterase↗

PubMed2005

Impact of environmental stressors on the dynamics of disease transmission.

Infectious disease within outmigrant juvenile salmon in the Columbia River Basin is modulated, in part, by abiotic stressors that influence host-susceptibility. Through the application of a dose-structured population dynamic model, we show that chemical (both in the river and in the estuary) and in-river (e.g., dams and/or predation) stressors influence host-susceptibility, increasing the mean force of infection (defined as the per capita acquisition rate of infection) by a factor of 2.2 and 1.6, respectively. Using Listonella anguillarum as a model pathogen, nonchemical in-river and chemical stressors contribute equally to a cumulative incidence of delayed disease-induced mortalities in Chinook salmon that range from 3% to 18% for estuary residence times of 30-120 days, respectively. Mitigation of environmental stressors that increase host-susceptibility could represent a significant component in future management strategies to recover listed stocks.

Animals↗

PubMed2005

Aryl hydrocarbon receptor-independent toxicity of weathered crude oil during fish development.

Polycyclic aromatic hydrocarbons (PAHs), derived largely from fossil fuels and their combustion, are pervasive contaminants in rivers, lakes, and nearshore marine habitats. Studies after the Exxon Valdez oil spill demonstrated that fish embryos exposed to low levels of PAHs in weathered crude oil develop a syndrome of edema and craniofacial and body axis defects. Although mechanisms leading to these defects are poorly understood, it is widely held that PAH toxicity is linked to aryl hydrocarbon receptor (AhR) binding and cytochrome P450 1A (CYP1A) induction. Using zebrafish embryos, we show that the weathered crude oil syndrome is distinct from the well-characterized AhR-dependent effects of dioxin toxicity. Blockade of AhR pathway components with antisense morpholino oligonucleotides demonstrated that the key developmental defects induced by weathered crude oil exposure are mediated by low-molecular-weight tricyclic PAHs through AhR-independent disruption of cardiovascular function and morphogenesis. These findings have multiple implications for the assessment of PAH impacts on coastal habitats.

Abnormalities, Multiple↗

PubMed2004

Defects in cardiac function precede morphological abnormalities in fish embryos exposed to polycyclic aromatic hydrocarbons.

Fish embryos exposed to complex mixtures of polycyclic aromatic hydrocarbons (PAHs) from petrogenic sources show a characteristic suite of abnormalities, including cardiac dysfunction, edema, spinal curvature, and reduction in the size of the jaw and other craniofacial structures. To elucidate the toxic mechanisms underlying these different defects, we exposed zebrafish (Danio rerio) embryos to seven non-alkylated PAHs, including five two- to four-ring compounds that are abundant in crude oil and two compounds less abundant in oil but informative for structure-activity relationships. We also analyzed two PAH mixtures that approximate the composition of crude oil at different stages of weathering. Exposure to the three-ring PAHs dibenzothiophene and phenanthrene alone was sufficient to induce the characteristic suite of defects, as was genetic ablation of cardiac function using a cardiac troponin T antisense morpholino oligonucleotide. The primary etiology of defects induced by dibenzothiophene or phenanthrene appears to be direct effects on cardiac conduction, which have secondary consequences for late stages of cardiac morphogenesis, kidney development, neural tube structure, and formation of the craniofacial skeleton. The relative toxicity of the different mixtures was directly proportional to the amount of phenanthrene, or the dibenzothiophene-phenanthrene total in the mixture. Pyrene, a four-ring PAH, induced a different syndrome of anemia, peripheral vascular defects, and neuronal cell death, similar to the effects previously described for potent aryl hydrocarbon receptor ligands. Therefore, different PAH compounds have distinct and specific effects on fish at early life history stages.

Abnormalities, Drug-Induced↗