Thesis (Ph. D.)--University of Kentucky, 2002. / Title from document title page. Document formatted into pages; contains vii, 158 p. : ill. Includes abstract. Includes bibliographical references (p. 128-155).

Endocrine-disrupting chemicals (EDCs) are environmental pollutants known to perturb hormone systems and interfere with normal endocrine function. Exposure to EDCs during hormone-sensitive developmental periods can result in profound dysfunction in reproductive physiology and behavior. In this dissertation, effects of gestational exposure to a class of EDCs called polychlorinated biphenyls (PCBs) were examined in the developing hypothalamus, which is known to control reproductive physiology and behavior in vertebrates. The specific hypothesis was that PCBs caused changes in sexually dimorphic hypothalamic nuclei, resulting in perturbation of adult sociosexual behaviors and alteration of neural networks with changes in expression of microRNAs and genes during development and in adulthood. This research focused on two brain areas relevant to understanding the PCB effects on the developing hypothalamus: 1) microRNA and related target gene expression during postnatal development, 2) adult sociosexual behaviors and gene expression. In both sections, molecular changes were examined in two sexually dimorphic hypothalamic nuclei, medial preoptic nucleus (MPN) and ventromedial nucleus (VMN), known for their role in regulation of sociosexual behavior. In the first section of the dissertation, the effects of PCBs were examined on the expression of microRNAs and target genes at four ages during postnatal [P] development (P15, P30, P45, and P90). Age and sex specific effects were observed in both MPN and VMN, with greater effects in the MPN. The second research section of the dissertation explored whether sociosexual behaviors, namely ultrasonic vocalizations and sociosexual preference behaviors, were altered by gestational PCBs. Expression of forty-eight neuroendocrine candidate genes was also examined in the MPN and VMN of the same animals. Several sociosexual behaviors were affected, including number and acoustic properties of ultrasonic vocalizations, and nose-touching with opposite-sex animals. Gene expression was altered in sex and region-specific manner in the brains of behaviorally affected rats. Taken together, these findings suggest that gestational PCBs have lasting effects on molecular mechanisms during postnatal development and in adulthood, and could result in altered sociosexual behavior. These results have implications for human health and disease, as early life exposures to EDCs have been linked to reproductive decline in humans. / text

Endocrine disrupting chemicals (EDCs) are a class of environmental toxicants, of both natural and synthetic origin, that interfere with normal endocrine function. Exposure to EDCs during susceptible periods of development, particularly embryogenesis, can result in profound neurological and reproductive deficits. While the impact of developmental exposure to EDCs on reproductive function and behavior has been much studied, the underlying mechanisms responsible for these observed effects are not well understood. The goal of the research detailed in this dissertation is to elucidate the cellular and molecular targets by which a representative class of EDCs, polychlorinated biphenyls (PCBs), disrupts normal reproductive neuroendocrine function. My specific hypothesis is that PCBs cause changes in sexually dimorphic brain regions underlying sex-specific reproductive physiology and behavior through the perturbation of normal developmental apoptosis, with long-term consequences for reproductive success. The studies detailed herein focus on three areas which contribute to an understanding of the effects of PCBs on neuroendocrine reproductive function: (1) the in vitro effects of PCBs on a neuroendocrine cell line, (2) developmental effects of PCBs on the gestationally exposed F1 generation, and (3) the physiological consequences of these developmental alterations for adult reproductive function. In the first section of this dissertation, the neurotoxic and endocrine disrupting effects of PCBs on a representative developing neuroendocrine cell model, the GT1-7 GnRH cell line, are investigated in time- and dose-response experiments. Treatment and dose-dependent effects are observed for GnRH peptide concentrations, cell viability, apoptotic and necrotic cell death, and caspase activation. In general, GnRH peptide levels are suppressed by high doses and longer durations of PCBs, and elevated at low doses and shorter time points. The suppression of GnRH peptide levels was partially reversed in cultures co-treated with the estrogen receptor antagonist ICI 182,780. All PCBs tested reduced viability and increased both apoptotic and necrotic cell death. The second section of this dissertation examines whether prenatal PCB exposure alters normal neuroendocrine development in the F1 generation, including sexual differentiation of the brain. Disruption of hypothalamic development is detectable as early as the day after birth (postnatal day (P) 1), as indicated by abnormal programmed cell death, and alterations in neuroendocrine gene and protein expression. The third section discusses the physiological impact of developmental PCB exposure on reproductive maturation and adult neuroendocrine function. Pubertal onset is advanced and estrous cyclicity irregular in PCB endocrine-disrupted females. Furthermore, sexual differentiation of female neuroendocrine systems is masculinized/defeminized. Collectively, these results suggest that the disrupted sexual differentiation of the POA can be detected as early as the day after birth, effects that may underlie the adult reproductive phenotype. / text

The primary objective of this study was to investigate the use of water table management (WTM) as a microbial delivery system for in-situ bioaugmentation of contaminated soils. In addition, the use of Rhizobium ( R.) for PCB degradation in soils was evaluated. / First, the presence and isolation of a variety of strains of Rhizobium meliloti was demonstrated using plant nodulation tests on alfalfa plants in soils that were contaminated for over 15 years with PCBs, PAHs and heavy metals. Next, R. meliloti, strain A-025, was selected based on its membrane (hydrophobicity, adhesion) characteristics and its potential to transform PCBs. This strain was delivered and implanted in sod columns, 200 mm in diameter x 1000 mm in length, packed with a sandy loam soil, using surface and subirrigation. The results of this study showed that subirrigation led to a higher number and a more uniform distribution of the bacterial cells in the soil at 60, 300, 500, and 700 mm depths, than surface irrigation. / In a different setup, similar column were packed with a PCB contaminated soil. These soil columns were bioaugmented with three bacterial cultures, i.e., R. meliloti (strain A-025), Comomonas testosteroni (strain B-356) and an indigenous bacterial consortium using subirrigation. The results indicated that bioaugmentation of the PCB contaminated soil was possible by using subirrigation. Bioaugmentation with the indigenous culture was observed to be more effective in the biodegradation of PCBs than with A-025 and B-356 cultures at 140 and 340 mm depths. However, at 590 mm depth, bioaugmentation with strain A-025 was observed to be better than the other treatments. Sequential aerobic and anaerobic cycles appear to be of significance for effective dechlorination of PCB congeners to lower chlorinated congeners. / In a separate exploratory study, the rhizospheric effects of alfalfa plants on R. meliloti for PCB depletion were investigated. The results suggest that the growth of alfalfa plants and bioaugmentation of soil with R. meliloti, strain A-025, increased the depletion of PCB congeners in the soil as compared to bioaugmentation alone. In other preliminary studies, the results showed that the presence of PCBs in a sandy loam soil increases the filtration of bacterial cells. Also, soil type and the presence of PCBs affected water infiltration, moisture, and hardness of the soil. Furthermore, water table management system along with bioaugmentation of soil columns with R. meliloti, strain A-025, decreased the concentration of atrazine by 31% during anaerobic and aerobic cycles and reduced the concentration of nitrate by 87% and 78% in the absence and presence of atrazine, respectively, in the drainage water. / The overall results of this work indicate that water table management (subirrigation) can be used for bioaugmentation of contaminated soils. Also, use of R. meliloti may prove to be an interesting option for soils contaminated with PCBs, atrazine and nitrate.

This study determines the effects of variations in suspended biomass, organic carbon, and pH on the time course of 2,2$ sp prime$,4,4$ sp prime$,5,5$ sp prime$-hexachlorobiphenyl uptake by laboratory cultures of Selenastrum capricornutum. Variations in pH had no effect, but uptake was enhanced by higher levels of biomass and depressed by higher levels of organic carbon. The coefficients for these measured effects on hexachlorobiphenyl were combined with existing relations based on molecular connectivity (X) or capacity ratio (K$ sp prime$) to yield semi-empirical equations to predict the instantaneous rate of uptake and bioconcentration factor (BCF) of organic contaminants as: eqalign{& rm Log rate = {-}3.30 + 0.32 X + 1.1 Log biomass {-}0.42 Log Abs cr& rm Log BCF = 4.11 + 0.86 Log K sp prime {-}0.87 Log biomass {-}0.22 Log Abs cr} / The utility of these equations was assessed by comparing time courses of hexachlorobiphenyl uptake predicted from them with time courses observed in water from eleven Quebec lakes.

No description available.

This study investigated the interaction between polychlorinated biphenyls (PCBs) and selenium to explain the mechanism involved that could affect selenium metabolism and its anti-cancer property. PCBs congeners and mixtures were previously found to reduce hepatic Se and Se-dependent glutathione peroxidase activity. I hypothesized that certain PCB congeners affect selenium metabolism in the rat liver resulting in diminished antioxidant capacity of selenoproteins, which could alter the ability of Se to protect against PCBs induced tumor promotion. In the first study, the influence of 3,3,4,4-tetrachlorobiphenyl (PCB 77) on hepatic Se and glutathione peroxidase (GPx1) activity as well as cytochrome P450 1A1 induction was examined by employing a time-course study, which showed that PCB 77 significantly reduced the hepatic selenium level and GPx1 activity and that this effect was influenced by gender. The next study explored how PCB 77 could deplete hepatic selenium by determining selenium concentrations in different tissues, feces and urine. This study demonstrated that PCB-77 decreased hepatic Se by increased excretion of Se in urine but not in feces. Unlike glutathione peroxidase, thioredoxin reductase activity was not affected by PCB 77. The third study investigated the effect of selenium supplementation on the tumor promoting activity of PCB 77 and 2,2,4,4,5,5-hexaclorobiphenyl (PCB 153) using a 2-stage carcinogenesis model. Se supplementation did not diminish the induction of altered hepatic foci by coplanar PCB 77 or ortho-substituted PCB 153. Instead of protection, the number of foci per cubic centimeter and per liver among the PCB-77 treated rats was increased as the selenium dietary level increased. PCB 153 did not show the same selenium dose-response effect; nevertheless, selenium supplementation did not confer protection against foci development. On the other hand, supranutritional selenium reduced the mean focal volume. Supranutritional selenium or PCBs did not affect cell proliferation or thioredoxin reductase activity. Lastly, the use of the Zeeman graphite furnace atomic absorption spectrometry (GFAAS) method and closed microwave digestion technique for selenium determination of biological samples was compared with the neutron activation analysis and fluorometry methods. I found that GFAAS was not as reliable as the other methods.

The National Electric Coil Company/Cooper Industries, Inc. plant in Harlan County, Kentucky was a mining support operation primarily engaged in the cleaning and repair of mining equipment from 1951 to 1987. Trichloroethylene (TCE) and degradation byproducts, polychlorinated biphenyls (PCBs), and vinyl chloride were released into the areas surrounding the plant periodically for decades. Routine water sampling of area wells by the Kentucky Department of Environmental Protection Division of Water revealed significant levels of TCE, PCBs, and vinyl chloride. The toxicology of these chemicals implicates various systems, including cardiovascular, dermal, endocrine, and neurological. University of Kentucky’s Superfund Basic Research Program’s (UK-SBRP) biomedical research is based on the premise that nutrition can modulate the effects of Superfund contaminants. In this study, the Community Outreach Core developed and delivered nutrition education programs to community members to address three issues: reduce total dietary fat, increase omega-3 fat, and increase dietary fiber. Initial efforts revealed the need for a holistic approach to identify and build trust with community members before programs could be presented. Results from informal discussions, qualitative assessments, and 24-hour dietary recalls using 2007 Nutrient Data System for Research were used to measure specific outcomes; increased knowledge, improved attitudes, and dietary behavior changes.

Polychlorinated biphenyls (PCBs) are toxic, stable organic contaminants that are present in air, water, soil, plants and animals all around the world. The market for PCB treatment technologies is estimated to be $300 to $600 million (Canadian dollars) for the year 2000, and will expand in future years. Existing treatment technologies to remove PCBs from soil are underutilized because they are more expensive than landfilling and incineration. This thesis presents a laboratory study of an innovative PCB remediation process that will extract PCBs from soil in-situ for subsequent destruction above ground. This remedy will remove PCBs from surficial soil without the need for excavation. Two laboratory studies were conducted on field-contaminated soil. The first experiment evaluated the effectiveness of hexane, methyl isobutyl ketone, and ethyl acetate in removing PCBs from soil. Ethyl acetate and MIBK were equally effective, removing 99% and 98% of PCBs from dry soil in 4 days, respectively. In the second experiment, soil was exposed to ethyl acetate for varying amounts of time, and some of the samples were treated a second time with fresh solvent. PCB removal increased as treatment time was increased from 10 minutes to 50, 250, and 1250 minutes, but the rate of PCB removal decreased as treatment time increased. The second 10-minute extraction removed an additional 1--10% of the remaining PCBs.

Polychlorinated biphenyls (PCBs) are a group of 209 chemical congeners that are toxic and persistent organic contaminants---they have been present in the environmental for several decades. Sites contaminated with PCBs pose serious health and safety risks to the surrounding environment due to their toxicity, persistence and bioaccumulation in creature. Polychlorinated biphenyls were commercially produced complex mixtures for a variety of applications. Before production was discontinued world-wide in 1977, several million tons of PCBs have been directly disposed to the soil. Researchers have been encouraged to develop novel techniques/approaches to detoxify PCB compounds and PCB contaminated soil. Ideally, these methods would be inexpensive, rapid, efficient and environmentally benign. / This study investigated novel approaches/techniques for PCB hydrodechlorination with noble metal catalyst in a continuous hydrogenation system, using a reactor column filled with Pd0/gamma-Al2O3 catalyst. Appreciable quantities of PCB compounds or other aromatic compounds were hydrodechlorinated and/or hydrogenated under mild conditions (90°C). The reaction efficiency was virtually complete if sufficient H2 was included in the mobile phase either by pure H2 or supercritical CO 2 combined with 5% H2. / The study also optimized conditions to wash PCBs washing condition from contaminated soil by sonication mixing and outlined an environmentally benign industrial application that combined soil washing with an at line PCBs hydrodechlorination process. The techniques/approaches developed in this study would seem to have a broad application in PCB dechlorination/detoxification and in the remediation of historically contaminated soil/sediments.