Two specific goals were addressed for this dissertation. First to investigate and identify the mechanistic profile of ketoconazole (KT)-induced hepatotoxicity by utilizing in vivo and in vitro approaches determining the mechanism of action for the hepatotoxicity incurred. To date, there has not been a mechanistic determination of the hepatotoxicity associated...
Reports of previous research indicated a stimulatory effect of
triazine herbicides on growth, yield and protein content of plants and
seeds of various species.
Studies were conducted in the greenhouse, laboratory and field
to investigate the effects of atrazine (2-chloro-4-ethylamino-6-a sopropylarnino-
s-triazine) on growth, yield, seed composition, and
seed germination...
In an experimental field study, populations of gray-tailed voles (Microtus canicaudus) were exposed to a commercial formulation of vinclozolin, a fungicide effective for disease control on ornamental plants, turf grasses, and fruits and vegetables. Vinclozolin has been shown in laboratory experiments to behave as an androgen antagonist, impairing the reproductive...
The aim of this study was to assess sensitivity of early life stage zebrafish to cadmium (Cd). Embryos and larva were exposed to Cd before the formation of skeletal elements. Exposure times were selected to determine whether Cd perturbed developmental processes that lead to skeletal deformities, and to characterize the...
Persistent organochlorines (OCs) bioaccumulate in aquatic biota and potentially impair reproduction via endocrine disruption. The present research evaluated estrogenic effects of the OCs, chlordecone (CD) and o,p'-DDT/DDE, and the antiestrogenicity of 3,4,5,3',4',5'-hexachlorobiphenyl (345-HCB) in juvenile rainbow trout, utilizing vitellogenesis as a biomarker. Vitellogenesis, estrogen regulated hepatic production of the yolk...
The toxic effects of degrading the chlorinated hydrocarbons trichloroethylene (TCE), chloroform (CF) and cis-1,2-dichloroethylene (cis-1,2-DCE) were studied in the bacterium Nitrosomonas europaea. N europaea is an ammonia-oxidizing bacterium that obtains all of its energy from the oxidation of ammonia to nitrite. This metabolic process involves two enzymes, ammonia monooxygenase (AMO)...
Numerous natural and anthropogenic chemicals interact with endocrine systems of
animals. The most widely studied of these endocrine active chemicals (EACs) are
estrogen receptor agonists and antagonists. Because of the many important roles of
estrogens in animals, xenoestrogens have the potential to impact environmental health. It
has been proposed that...
Liver X receptor (LXR), farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) are adopted orphan nuclear receptors that function as lipid sensors. These receptors respond to cellular lipid levels and regulate the expression of target gene. Previously, it was demonstrated that low doses of chlordecone (CD) pretreatment disturbed exogenous...
Lymphomas and leukemias are the most common cancer in children and young adults and in utero exposure to carcinogens may contribute to the etiology of these cancers. A polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), was administered to pregnant mice (15 mg/Kg b.w., gavage) on gestation day 17. Significant mortalities in...
Mercury and arsenic are known developmental toxicants and environmental exposures are ubiquitous worldwide from natural and anthropogenic sources. Prenatal exposure to both contaminants are independently associated with adverse perinatal health outcomes and latent disease risk that could be in part mediated by epigenetic reprogramming events. Fetal programming events involving DNA...
Pacific lamprey (Entosphenus tridentatus) are experiencing population declines throughout their range. Xenobiotics could be an important risk factor for lamprey populations. Our goal was to establish if common herbicides, as used in forest management, could affect reproductive fitness. We determined that atrazine was a likely compound of greatest concern to...
Female mink (Mustela vison) are highly sensitive to polychlorinated biphenyl (PCB)-induced reproductive impairment. The goal of this research was to develop a better understanding of the mechanism of PCB-induced effects on female mink, mink embryos, and surviving mink kits. Anestrous, juvenile female mink and pregnant, adult mink were exposed to...
Two factorial experiments were conducted to determine if
high dietary fluoride would inhibit selenite toxicity in
rats. In each study, two levels of selenite (0.05 and 5
mg/kg diet) were matched against two levels of fluoride (1
and 150 mg/kg diet) for either 6 or 8 weeks. Fluoride failed
to...
Chilling requirements of 43 apple and 38 pear cultivars
were estimated over a 2 year period by cutting shoots in the
field at weekly intervals and forcing them in a warm
greenhouse for 4 weeks. For apples, the mean values ranged
from 490 Chill Units (CU) +- 1 for 'Dorsett...
Great blue heron (Ardea herodias) eggs and prey items were collected from six colonies on the Columbia and Willamette rivers and Puget Sound during 1994-95. Contaminant concentrations, reproductive success, and biomagnification factors (BMFs) were determined and effects of residue levels were measured by H4IIE rat hepatoma and ethoxyresorufin-O-dealkylase (EROD) bioassays....
Internal dosimetry is challenging and relies on estimates using MIRD or ICRP biokinetic models. To address this, we looked at gene expression analysis in whole blood from radiotherapy patients. Patients with relapsed or refractory neuroblastoma who received ¹³¹I-mIBG at UCSF were used to correlate internal ionizing radiation (IR) dose with...
During the past 30 years, numerous studies have focused on the toxicities of polycyclic aromatic hydrocarbons (PAH). Laboratory and field studies have helped elucidate the detrimental effects of these chemicals on growth, reproduction and immune response. Polycyclic aromatic hydrocarbons are in the priority list of chemicals to be studied by...
Detection of both biological and chemical environmental toxicants is essential in the assessment of risk to human health. Cell-based biosensors are capable of activity- based detection of toxicity. Chromatophore cells, responsible for the pigmentation of poikilothermic animal, have shown immense potential as cell-based biosensors in the detection of a broad...
This study was part of the Antarctic Environment and Southern Ocean Study (AESOPS) program, whose main goal was to investigate the role of the biota in the carbon flux from the atmosphere to the interior of the ocean. We quantified the abundance of the major phytoplankton classes and examined the...
Natural and synthetic estrogenic compounds detected in surface waters have
been linked to endocrine signaling disruption in several species. Endogenous
estrogen contributes to cartilage and bone deposition during development in
vertebrates, and is susceptible to perturbation from xenoestrogens. The goals of
this work were to develop a teleost model to...
This study was undertaken to determine if strontium chloride could be used to create a trans-generational otolith mark in steelhead (Oncorhynchus mykiss). I completed two strontium injection trials and a survey of juvenile steelhead from various steelhead hatcheries. The two trials measured Sr:Ca ratios in otoliths in response to injections...
The atmospheric transport and deposition of semi-volatile organic compounds (SOCs), including current and historic use pesticides, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), to mountain ecosystems may result in the exposure of tadpoles to these SOCs. This exposure has been implicated in amphibian population declines in California. Tadpoles encounter...
The human health effects of exposure to numerous single environmental contaminants have been well characterized. Yet, biomonitoring studies have detected multiple environmental chemicals in humans, highlighting the need to investigate the health effects of exposure to multiple environmental chemicals. Environmental data is highly complex, therefore current methods of defining environmental...
Many studies addressing the toxicity of silver nanomaterials have found that smaller sized silver nanoparticles are usually more toxic to organisms and in cell culture than particles of larger sizes yet it is not entirely clear why. We investigated the size dependent toxicity of silver nanoparticles by measuring the response...
Fluorinated chemicals (FCs) have been used since the 1950s in many industrial and commercial applications because of their unique properties such as chemical inertness, resistance to heat and their ability to repel water and oils. Concerns regarding potential environmental or human health risk from FCs exposure have emerged due to...
Polycyclic aromatic hydrocarbons (PAHs) are significant pollutants in aquatic environments. Many are carcinogenic and lead to DNA fragmentation and adduct formation in marine and freshwater organisms. Previous research demonstrates that rainbow trout (Oncorhynchus mykiss) compensate to long-term PAH dietary exposures and reduce the DNA damage.
The aim of this study...
Laboratories around the world are using the zebrafish model for biomedical research and conducting investigations using morphological, physiological, behavioral, and genomic endpoints. All assays provide information, but physiological and behavioral endpoints or phenotypes are a fast way to understand how an animal is responding to its environment. We investigate the...
Rainbow trout (Oncorhynchus mykiss) experience a variety of stressors in their natural environment as well as in aquaculture that can have negative effects on their physiology. The effects of physiological stress and endocrine disruption have been well described in fish. However, there is a scarcity of information on the effects...
The upper drainage of the John Day River system produces summer steelhead and spring chinook salmon. The fish are generally confined to the main stem and its tributaries above Prairie City. The spawning and rearing areas are comparatively free of undesirable fish species, but salmonid smolts migrating downstream must travel...
The potential impact of chemical contaminants and conservation practices on amphibians in agricultural landscapes is a key research topic globally. Amphibians represent a common group in many freshwater systems and are currently experiencing worldwide population declines. Global amphibian declines may be attributed to a number of causes, including habitat loss,...
A large number of river otter (Lontra canadensis) males were collected
from areas of high and low contaminant concentrations throughout western
Oregon and Washington during the fall and winter of 1994-99. Few significant
non-reproductive organ morphometric differences were found in the large series
of male otters collected, except for adrenal...
A large number of river otter (Lontra canadensis) males were collected
from areas of high and low contaminant concentrations throughout western
Oregon and Washington during the fall and winter of 1994-99. Few significant
non-reproductive organ morphometric differences were found in the large series
of male otters collected, except for adrenal...
Many pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers
(PBDEs), and polycyclic aromatic hydrocarbons are persistent, bio-accumulative, and
toxic. These semi-volatile organic compounds (SOCs) can undergo atmospheric
transport and deposition in cold, remote ecosystems. A better understanding of their
accumulation in the fish of these ecosystems is important to better predict...