The mechanism of gossypol acetic acid cytotoxicity /
Gossypol is toxic to humans and animals, and has several potential therapeutic uses. The biochemical mechanisms by which gossypol exerts cytotoxic effects were studied in the present dissertation. In the first phase of these experiments, vital fluorescence microscopy was used to noninvasively moni...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1998.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=737704031&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Gossypol is toxic to humans and animals, and has several potential therapeutic uses. The biochemical mechanisms by which gossypol exerts cytotoxic effects were studied in the present dissertation. In the first phase of these experiments, vital fluorescence microscopy was used to noninvasively monitor multiple physiological endpoints in living cells after exposure to gossypol. In short term steady state (two hours treatment) and kinetic (acute) analyses, gossypol was shown to decrease mitochondrial membrane potential, plasma membrane potential, gap junctional intercellular communication, and to increase cytoplasmic calcium ion levels. In the second phase of these experiments, agents that increased gap Functional intercellular communication or antioxidants were tested for their ability to attenuate the cytotoxic response to gossypol. In long term (48 hour) cellular proliferation assays, 8-bromo-cyclic adenosine monophosphate, an agent known to increase gap junctional intercellular communication, was shown to attenuate gossypol cytotoxicity more dramatically than other agents tested. In vital fluorescence microscopy assays and immunoblots. 8-bromo-cyclic adenosine monophosphate attenuated gossypol's cytotoxic effects on the following parameters: inhibition of gap junctional intercellular communication, degradation of gap junctional subunits, production of reactive oxygen species, cytoplasmic acidification, reduction in cellular glutathione levels, and increased cytoplasmic calcium ion levels. In the third phase of these experiments, c-fos, a component of a redox-sensitive transcription factor, was found to be induced in response to gossypol. Subtractive hybridization was used to detect two other genes, c@-cytochrome c oxidase subunits I and 11, that studies represent a comprehensive analysis of the biochemical and genetic mechanisms of gossypol cytotoxicty. |
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| Item Description: | Vita. "Major Subject: Veterinary Anatomy". |
| Physical Description: | x, 140 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references: pages 101-131. |