Cellular fingerprinting of 2,3,7,8-tetrachlorodibenzo-para-dioxin as a neurotoxicant /
Halogenated aromatic hydrocarbons (HAHS) are the focus of great media and public concern, based on the fact that some congeners produce extreme toxicity in laboratory animal studies. In addition, these compounds are ubiquitous in the environment and food chain. While much attention has been given...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1995.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=742145381&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Halogenated aromatic hydrocarbons (HAHS) are the focus of great media and public concern, based on the fact that some congeners produce extreme toxicity in laboratory animal studies. In addition, these compounds are ubiquitous in the environment and food chain. While much attention has been given to the carcinogenicity of HAHs little work has been done in the area of neurotoxicology. Therefore, the focus of this dissertation was to analyze neurochemical and functional endpoints as indicators of neurotoxicity, resulting from in-vitro exposure of low-levels of HAHs including polychlorinated biphenyis (PCBS) and polychlorinated dibenzo-p-dioxins (PCDDs). Data collected in this dissertation indicates that rat neurons and astroglia respond to a variety of toxic insults by a limited number of cellular events, including disruption of normal calcium homeostasis, reduction of cellular glutathione content, perturbations of mitochondrial membrane potential and alteration of biochemical signal transduction., We observed that both neurons and astroglias showed robust changes in calcium signaling which produced down-stream changes in protein kinase C (PKC) and glutamine synthetase (GS). These changes are consistent with the identification of the 9-10S cytosolic Ah receptor in astroglia and C6 glioma cells, yet the data presented from diverse antagonist Dharmacology studies, suggest that the effects seen are significantly different from other Ahmediated responses. Moreover, mechanistic studies conducted in this dissertation suggest that in the C6 rat glioblastoma cell line, that TCDD alters normal muscarinic cholinergic receptor-mediated calcium release, which further suggests that TCDD may also interact with cell surface receptors in a similar fashion as do steroid hormones such as estrogen. Current studies are still needed to further elucidate cell membrane targets for 2,3,7,8-TCDD, however, data collected in these studies indicate that there may be both an Ah-dependent pathway as well as an Ah-independent pathway associated with neurochemical changes during HAH exposure. |
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| Item Description: | Vita. "Major Subject: Toxicology". In title, numerals are used. |
| Physical Description: | xi, 112 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references. |