Structure-activity relationships for halogenated aromatic hydrocarbons and related compounds : induction of cytochrome P450 isozymes and antiestrogenic activities in rats /
Initial studies characterized dose-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat liver, lung, and kidney, with special attention to the effects of low doses (1 to 100 ng/kg). Induction of P4501A1-dependent ethoxyresorufin O-deethylase (EROD) activity, accumulation of nuclea...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1996.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=739667401&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Initial studies characterized dose-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat liver, lung, and kidney, with special attention to the effects of low doses (1 to 100 ng/kg). Induction of P4501A1-dependent ethoxyresorufin O-deethylase (EROD) activity, accumulation of nuclear [3H]TCDD-Ah receptor complex , and CYP1A1 and CYP1A2 mRNA levels were observed at [3H]TCDD doses > 500 ng/kg. The tissues examined exhibited similar sensitivities to TCDD although the magnitude of the responses followed a rank order: liver >> kidney > lung. The relative potencies of five commercial PCB Aroclor mixtures as inducers of EROD activity following a rank-order: Aroclor 1254 > 1242 > 1248 > 1260 > 1016 in B6C3F1 mice; and Aroclor 1260 > 1254 > 1248 > 1242 > 1016 in Sprague Dawley rats. ED50 values were in a range of 354 - 841 mg/kg. Individual PCB congeners identified as major toxic components of Aroclor were also tested as inducers of EROD activity in rats, and ED50 values for these congeners were utilized to derive 'calculated' potencies for 4 Aroclors. 'Experimental' and 'calculated' values did not always compare, suggesting that PCBs within these mixtures may interact to modulate the induction potencies of these mixtures. Dose-dependent effects of 18 ortho-substituted PCB congeners and 4 Aroclor mixtures as inducers of P4502B1-dependent hepatic pentoxyresorufin-O-dealkylase (PROD) activity were determined in rats 3 d after ip injection. At a 150 mg/kg dose, potencies of the Aroclor mixtures followed the rank-order: 1260 [] 1254 > 1242 > 1016. |
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| Item Description: | Vita. "Major Subject: Toxicology". |
| Physical Description: | xiv, 165 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references: pages 138-164. |