Thyrotoxic and dopaminergic effects of polychlorinated biphenyls
Ness, Daniel Keith
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Permalink
https://hdl.handle.net/2142/21432
Description
Title
Thyrotoxic and dopaminergic effects of polychlorinated biphenyls
Author(s)
Ness, Daniel Keith
Issue Date
1994
Doctoral Committee Chair(s)
Beasley, Val Richard
Department of Study
Veterinary Medicine
Discipline
Pathobiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Toxicology
Environmental Sciences
Language
eng
Abstract
Perturbations in the developing nervous system have been associated with perinatal exposures to polychlorinated biphenyls (PCBs). To determine which PCBs accumulate in brain following perinatal exposure, Sprague-Dawley rats were exposed by gavage to Aroclor 1242 (4 or 16 mg/kg/day) during days 10-16 of gestation. At weaning (day 21), analysis of pup brain (frontal cortex, hippocampus, and caudate putamen) by gas chromatography revealed ten peaks representing 10-14 congeners in PCB-exposed animals. Brain PCB concentrations were greatest in high-dose pups for all congeners except for 2,4,4$\sp\prime$-trichlorobiphenyl (PCB 28) which had a higher concentration in the low-dose group. Congeners differed significantly in their degree of bioaccumulation, but no significant differences among brain regions were found. A lack of regionalization of PCB residues in the brain was also demonstrated by autoradiography in weanling rats treated iv with ($\sp{14}$C) -3,3$\sp\prime$,4,4$\sp\prime$-tetrachlorobiphenyl or ($\sp{14}$C) -2,2$\sp\prime$4,4$\sp\prime$-tetrachlorobiphenyl.
Time-mated Sprague-Dawley rats were exposed on days 10-16 of gestation to three environmentally-relevant PCBs: 2,4,4$\sp\prime$-trichlorobiphenyl (PCB 28), 8 or 32 mg/kg/day; 2,3$\sp\prime,$4,4$\sp\prime,$5-pentachlorobiphenyl (PCB 118), 4 or 16 mg/kg/day; or 2,2$\sp\prime$4,4$\sp\prime$5,5$\sp\prime$-hexachlorobiphenyl (PCB 153), 16 or 64 mg/kg/day. At weaning, serum total thyroxin, but not triiodothyronine, was markedly depressed in pups exposed perinatally to PCB 118 or 153; and thyroid glands from PCB 118-treated pups revealed histologic changes suggestive of sustained TSH stimulation. No significant PCB-induced changes were detected in the activity of the rate limiting enzyme in the synthesis of catecholamines, tyrosine hydroxylase, in the caudate putamen at weaning or in adulthood. Likewise no significant changes were detected in dopamine receptor (D1 and D2) concentrations in several regions in the mesocortical and nigrostriatal pathways.
Utilizing a tritium release assay, no inhibition of rat caudate putamen tyrosine hydroxylase activity by Aroclor 1242 was detected in vitro. While planaria (Dugesia dorotocephala) exposed to a known tyrosine hydroxylase inhibitor, 3-iodo-L-tyrosine, demonstrated both decreased head dopamine concentrations and eye pigmentation (presumably melanin), exposure of planaria to Aroclor 1242 resulted in only a decrease in head dopamine concentration. These data are consistent with other studies associating PCB exposure and decreased dopamine synthesis; however, inhibition of tyrosine hydroxylase was not observed.
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