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Antiestrogenic and immunotoxic effects of polychlorinated dibenzo-p-dioxins and dibenzofurans : mechanistic studies
Abstract
Polychlorinated dibenzo-p-dioxins and dibenzofurans are environmental contaminants which elicit a number of toxic and biochemical effects including immunotoxicity, hepatic microsomal monooxygenase induction and enodcrine effects. The dose-response effects of 4 heptachlorodibenzofurans (HpCDF) on the splenic plaque forming cell (PFC) response to sheep erythrocytes and on the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-Odeethylase (EROD) were determined in male C57B1/6 mice. The 2,3,7,8-substituted HpCDF isomers (1,2,3,4,6,7,8- and 1,2,3,4,7,8,9-HpCDF) were significantly more potent than the isomers which contained only three lateral chlorine groups and the results were similar using either a multiple dosing (10) or a single dosing regimen. The 2.3.7.8-substituted HpCDFs were approximately one-tenth as potent as 2,3,7,8- tetrachloro-dibenzo-p-dioxin (2,3,7,8-TCDD). The antiestrogenic activity of 15 alkylated dibenzo-p-dioxins and dibenzofurans were investigated in the female Sprague-Dawley rat uterus. All of the compounds tested exhibited similar antiestrogenic potencies, however one congener, namely 6-isopropyl1.3.8-trichlorodibenzofuran showed relatively high antiestrogenic potency but was a poor inducer of hepatic microsomal EROD activity (a measure of toxicity). The estrogenic properties of 6-nitro-1,3,8-trichlorodibenzofuran (6-NCDF) were also investigated. Administration of 6-NCDF caused a dose- and time-dependent increase in uterine wet weight, cytosolic and nuclear estrogen (ER) and progesterone receptor (PR) levels in immature female Sprague-Dawley rats. In contrast, 6-NCDF did not increase uterine peroxidase or epidermal growth factor receptor binding activities. 2.3.7.8-TCDD, a known antiestrogen inhibited the uterotrophic effect but not the increase in uterine ER and PR binding activity induced by 6-NCDF. 6-NCDF competitively bound to the uterine Ah receptor but not to the ER or the PR. The effects of 2,3,7,8-TCDD on androgen receptor binding were measured in both male and female Sprague-Dawley rats. 2,3,7,8-TCDD caused a significant increase in the AR binding activity in the urogenital sinus of adult male rats. In 21-day old male and female rats, 2,3,7,8-TCDD caused a significant increase in the cytosolic AR binding in the testes and the uterus.
Description
Typescript (photocopy).Subject
Major toxicology1992 Dissertation D549
Polychlorinated dibenzodioxins
Toxicology
Polychlorinated dibenzofurans
Toxicology
Estrogen
Antagonists
Immunotoxicology
Collections
Citation
Dickerson, Richard Lee (1992). Antiestrogenic and immunotoxic effects of polychlorinated dibenzo-p-dioxins and dibenzofurans : mechanistic studies. Texas A&M University. Texas A&M University. Libraries. Available electronically from https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -1281176.
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