The biologic and toxic effects of halogenated hydrocarbons in the guinea pig and Sprague-Dawley rat /
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| Other Authors: | , , |
| Format: | Thesis Book |
| Language: | English |
| Published: |
1988.
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| Subjects: | |
| Online Access: | ProQuest, Abstract Link to OAKTrust copy |
| Abstract: | The dose-response effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,4,7,8-pentachlorodibenzo-pdioxin, 2,3,4,7,8 -, 1,2,3,7,9-, 1,2,3,7,8- and 2,3,4,7,9-pentachlorodibenzofuran on body weight loss and hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin 0-deethylase (EROD) induction were determined in the immature male guinea pig. The most toxic congener in this series was 2 ,3,7,8 -tetrachlorodibenzo-p-dioxin (2,3,7,8 -TCDD) in which the in vivo (guinea pig) ED[50] values for AHH and EROD induction and body weight loss were 0.09, 0.03 and 1.8 ug/kg respectively. Also, the effects of 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP), (0.10 g/kg) on the enzyme induction responses of 2,3,7,8-TCDD (0.05 ug/kg, 1.0 ug/kg or 4 ug/kg) were investigated by co-treatment of guinea pigs with 2,3,7,8-TCDD plus HCBP followed by measuring the magnitude of AHH and EROD induction responses. Higher dose levels of 2,3,7,8-TCDD (1 or 4 ug/kg) resulted in maximally induced hepatic microsomal AHH (446 pmol/mg protein/min) and EROD (464 pmol/mg protein/min) and co-treatment of guinea pigs with HCBP (0.10 g/kg) did not alter the magnitude of AHH and EROD induction. Moreover, co-treatment of guinea pigs with a known 2,3,7,8-TCDD antagonist, 6-methyl-l,3,8-trichlorodibenzofuran (0,01 g/kg) resulted in enzyme activities which were not significantly different from those values observed after treatment with 2,3,7,8-TCDD alone. In addition, the effects of 2,3,7,8,-TCDD (10 ug/kg) on the growth of 7,12-dimethylbenz(a)anthracene-induced (DMBA-induced) mammary tumors in female Sprague-Dawley rats was investigated. 2.3.7.8-TCDD caused a significant delay in the onset of DMBA-induced tumors and the co-treatment of rats with 2,3,7,8-TCDD at a dose level of DMBA of 20 mg/rat resulted in only 10% of the rats (1/10) with tumors after 120 days. Treatment of rats with DMBA alone resulted in a 50% (5/10) tumor yield on day 120. In a subsequent study, a group of 40 rats with mammary tumors were either untreated or treated with 2.3.7.8-TCDD (10 ug/kg). It was apparent that after 21 days, 2.3.7.8-TCDD was acting as a potent antitumorigenic agent. |
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| Item Description: | Typescript (photocopy). Vita. "Major subject: Toxicology." |
| Physical Description: | xiii, 153 leaves : illustrations ; 29 cm |
| Bibliography: | Includes bibliographical references (leaves 135-152). |