Complex mixtures of polynuclear aromatic hydrocarbons as Ah receptor agonists /
| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[Place of publication not identified] :
[publisher not identified] ;
1994.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=741964921&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Item Description: | Vita. "Major Subject: Toxicology". |
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| Physical Description: | xiv, 170 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. Many of the carcinogenic polynuclear aromatic hydrocarbons (PAHS) bind to the Ali receptor and elicit a broad spectrum of Ali receptor-mediated responses including: induction of CYPIAI and CYPIA2 gene expression, induction of other drug metabolizing enzymes, decrease in glucocorticoid receptor binding activity, downregulation of epidermal growth factor binding activity, and inhibition of 17 0estradiol-induced responses in MCF-7 human breast cancer cell lilies. Since P- 450 isozymes play an important role in the subsequent formation of carcinogenic and noncarcinogenic PAH metabolites, it was of interest to characterize the activity of Manufactured Gas Plant residue (MGP), a complex mixture of PAHS, and its reconstituted and structural fractions as inducers of CYPIAL and CYPlA2 gene expression. The MGP PAH mixture exhibited non-additive (synergistic) activities as an Ali receptor for several in vivo and in vitro responses, and the reason for these apparent non additive interactive effects are unknown. However, they are not related to contamination by trace levels of TCDD and related compounds as determined by GC/MS analysis. Both the reconstituted and > 4-ring PAH mixtures induce EROD activity and CYPlAl protein and MRNA levels in liver and exhibit significantly lower activity in lung; whereas 3-ring and 2-ring PAHs were relatively inactive as CYPlAl inducers. In addition, both the reconstituted and > 4- ring PAH mixtures induced CYPIA2 gene activity; however, activity of the reconstituted PAH mixture was higher than observed for > 4-ring PAHS, suggesting that the 3- or 2- ring PAHs may induce CYPlA2. Furthermore, it was shown that the 3-ring PAHs induce hepatic MROD activity, and CYPIA2 protein and MRNA levels, and, among the PAH fractions, this fraction was the most active inducer of MROD activity at all doses tested. Infrared laser induced photodesorption of small alcohols (Cl - C4) on Ag (1 I 1) was studied using C-H excitation (2800- 30OOcnf') and 0-H excitation (3100-35OOcnf 1). The photodesorption yield (PDY) depended on a number of factors including the mode of excitation, the annealing temperature, the wavelength of the laser, the laser intensity, and the film thickness. The PDY spectrum showed peaks at -3310cm-', -2880cm-1 and -2970cm-'. These were assigned as the 0-H stretching mode, and the symmetric and antisynimetric C-H stretching modes, respectively. The PDY increased with the total amount of energy absorbed by the adsorbate film and decreased with the molecular weight of the alcohol molecules. The kinetic energies of the desorbing flux were determined by fitting the time-resolved photodesorption signal with a modified Maxwellian velocity distribution. Conditions which resulted in high PDY also gave high kinetic energies, which ranged from 10-25kJ/mol. The photodesorption signals resulting from C-H excitation were very similar to those from 0-H excitation. However, the PDY was smaller, and the kinetic energy was higher when the C-H vibrational modes of the alcohol molecules were excited. The observed results were inconsistent with either the resonant heating or the direct mechanism. A non-thermal mechanism, which incorporates both the resonant heating and the direct mechanisms, is suggested. |
| Bibliography: | Includes bibliographical references. |