Halogenated aromatic hydrocarbons : mechanistic studies /
| Main Author: | |
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| Other Authors: | , , |
| Format: | Thesis Book |
| Language: | English |
| Published: |
1990.
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| Subjects: | |
| Online Access: | ProQuest, Abstract Link to OAKTrust copy |
| Abstract: | Halogenated aromatic hydrocarbons (HAHs) elicit a broad range of biochemical responses and these include antiestrogenic effects and the induction of cytochrome P450-dependent monooxygenases. One component of this research probed the role of several factors in the induction of monooxygenase enzyme activities and these included: (a) the role of the 4S binding protein (b) the mechanisms associated with the antagonism of 2,3,7,8-TCDD-induced rat hepatic microsomal AHH and EROD activity by MCDF and (c) structure-dependent induction of AHH and EROD activity. A second area of research investigated the mechanism of HAH-mediated antiestrogenicity in human breast cancer cells. The results from these studies suggest that the 4S binding protein does not play a role in the induction of AHH and EROD activity by PAHs. Based on the relative affinities of several inducers for the 4S binding protein and the Ah receptor, a correlation was observed between their Ah receptor binding affinities and their potencies as inducers of AHH and EROD activity. The mechanism of MCDF as an 2,3,7,8-TCDD antagonist was investigated by measuring the accumulation of nuclear [3H] -2,3,7,8-TCDD-Ah receptor complexes in the hepatic tissue in the presence or absence of MCDF. MCDF did not effect the accumulation of nuclear Ah receptor complexes however, MCDF inhibited the replenishment of the cytosolic Ah receptor. The structure-dependent induction of hepatic microsomal AHH and EROD activity in C57BL/6 mice by a series of radiolabeled agonists showed that the levels of radioligand-Ah receptor complexes which accumulated in the nucleus were structure-dependent. Moreover, there was correlation between the levels of nuclear Ah receptor complexes and the induced AHH and EROD activity in hepatic tissue. These results suggest that the formation of the activated cytosolic Ah receptor may be an important structure-dependent effect in the induction process. The antiestrogenic studies resulted in the characterization of two Ah responsive cell lines namely, MCF-7 and T-47D human breast cancer cells. Moreover, the results of several studies on the effects of 2,3,7,8-TCDD and related HAHs on the reduction of the nuclear estrogen receptor complex suggests that this response is also Ah receptor-mediated. |
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| Item Description: | Typescript (photocopy). Vita. "Major subject: Toxicology." |
| Physical Description: | xvi, 145 leaves : illustrations ; 29 cm |
| Bibliography: | Includes bibliographical references. |