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|Title:||Effects of polychlorinated biphenyls (PCBs) on hepatic enzyme induction, uterotropic responses, and thyroid hormone levels in prepubertal female rats|
|Doctoral Committee Chair(s):||Hansen, Larry G.|
|Department / Program:||Veterinary Biosciences|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Subject(s):||Health Sciences, Toxicology
|Abstract:||A 2-day short-term bioassay, using prepubertal female Sprague-Dawley rats, was developed to study effects of polychlorinated biphenyls (PCBs) on hepatic enzyme induction, uterotropic responses, and thyroid hormone levels. Three approaches have been used to study the multiple effects of PCB mixtures: (1) environmental mixtures (soil, dust and air samples) collected from the Sangamo landfill site were directly examined and the chemical compositions of these mixtures were analyzed; (2) the soil extract from the Sangamo landfill site was fractionated by alumina-charcoal column chromatography, the effects of this fraction were tested, and the results were compared with the effects of the original soil extract; (3) a combination of specific chlorobiphenyls (CBs) (2,3,3$\sp\prime,4\sp\prime$,6-pentachlorobiphenyl (CB 110) plus 3,3$\sp\prime,4,4\sp\prime$,5-pentachlorobiphenyl (CB 126)) and a synthetic mixture which contained 95.5% CB 110, 0.5% CB 126 and 4% two unidentified pentaCBs were also examined. In addition, the effects of 3 environmentally abundant di-ortho CBs (2,2$\sp\prime,4,4\sp\prime,5,5\sp\prime$-hexachlorobiphenyl (CB 153), 2,2$\sp\prime$,5-trichlorobiphenyl (CB 18) and CB 110) were examined.
None of the 3 individual CBs induced P4501A activity, whereas CB 153 and CB 110 markedly induced P4502B activity. All 3 CBs produced uterotropic responses at least at one or more of the doses tested. CB 153 was the most estrogenic of the 3 CBs tested. All 3 CBs slightly reduced serum total thyroxine (T$\sb4$) in prepubertal rats, but these reductions were not statistically significant at up to 120 mg/kg. In addition, the level of serum CB residues in prepubertal rats was considerable higher than would be expected of adult rats at similar doses.
All PCB mixtures studied were able to induce both P4501A and 2B activities as well as 4-nitrophenol UDP glucuronosyltransferase (4-NP UDPGT) activity. All mixtures examined effectively depressed serum total T$\sb4$ to less than 50% of controls at higher doses and dose:response relationships were very similar despite significant differences in proportions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like compounds and non-TCDD-like compounds in the mixtures. The mixtures containing lower proportions of TCDD-like compounds (such as the air extract collected from the Sangamo landfill site and the charcoal-filtered soil extract) were more estrogenic than the mixtures containing greater amounts of TCDD-like compounds. Some antagonistic effects were observed in P450 enzyme activity as well as uterotropic responses between the mixtures containing TCDD-like compounds and non-TCDD-like compounds. These results indicate that both TCDD-like and non-TCDD-like effects of PCBs should be considered in assessing the potential hazards of environmental PCB mixtures.
|Rights Information:||Copyright 1996 Li, Mei-Hui|
|Date Available in IDEALS:||2011-05-07|
|Identifier in Online Catalog:||AAI9625157|
This item appears in the following Collection(s)
Graduate Dissertations and Theses at Illinois
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Comparative Biosciences