Interactive effects of environmentally relevant polychlorinated biphenyls and dioxins on [3H]phorbol ester binding in rat cerebellar granule cells.

Abstract

[3,3',4,] did not alter the in vitro activity of the noncoplanar (2,2',5,5'-TeCB) or coplanar [4,4'-dichlorobiphenyl (DCB)] congeners; 2) binary mixtures of active PCB congeners (2,2',4,4'-TeCB and 2,2'-DCB; 2,2'-DCB and 3,5-DCB; 2,2',3,5',6-PeCB and 2,2',4,4',5-PeCB) interact in a dose-additive manner; 3) TCDD did not alter the activity of either coplanar (3,3',4,4'-TeCB) or noncoplanar (2,2',5,5'-TeCB) congeners; 4) the interaction between the parent PCB congener and hydroxy metabolite of PCB is additive; 5) PCB congener mi at the ratios found in environmental samples are biologically active; and 6) there was no indication of synergism in any of the combinations studied. These results sugst that the biological effet of binary mixtures of PCB congeners fit a dose-additive model, indicating that there is a specific site of action for these PCB congeners which is independent of the aryl hydrocarbon receptor.

Potentiation of the Human GABAA Receptor As a Novel Mode of Action of Lower-Chlorinated Non-Dioxin-Like PCBs

“…Similarly, inhibition of membrane transporter-mediated neurotransmitter uptake is also specifically inhibited by ortho-substituted PCBs, with tetra- and penta-chlorinated PCBs showing the strongest inhibition . Further, PCB-induced ryanodine receptor activation , Protein Kinase C (PKC) translocation − , and decrease in cell dopamine content appeared again specific for ortho-substituted PCBs, with penta-chlorinated congeners, especially PCB153, being among the most potent PCBs. Disruption of Ca 2+ homeostasis has been identified as one of the major neurotoxic effects of NDL-PCBs − , with penta- and hexa-chlorinated congeners among the most effective PCBs .…”

Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

“…PCBs produce changes in a number of behavioral domains in humans and animals ( Rice 2000 ; Schantz et al 2003 ). They also affect multiple neurochemical pathways ( Kodavanti et al 1993 ; Kodavanti and Ward 1998 ; Seegal 1996 ; Seegal et al 1991 ) in addition to TH ( Crofton and Zoeller 2005 ). Although changes in THs during development predict specific behavioral changes, effects of PCBs on some specific tasks in animals or outcomes in epidemiologic studies may not necessarily be attributable to changes in THs.…”

Differential gene expression and a functional analysis of PCB-exposed children: Understanding disease and disorder development

“…Congener- and concentration-dependent antagonism of 17beta-estradiol (E2)-induced gene expression, rather than the induction of ER-dependent gene expression, was observed for the MeSO (2)-PCBs (2, 2′, 4, 5, 5′-pentachlorobiphenyl) (PCB-101) and 2, 2′, 4, 5′-tetrachlorobiphenyl (CB49) on lucifierase activity in stably transfected human breast adenocarcinoma T47D cells (ER-CALUX) (Letcher et al, 2002). A considerable literature exists on neurobehavioral toxicity resulting from pre- and post-natal exposures to PCBs performed in animal studies (Kodavanti et al, 1998; Lilienthal & Winneke, 1991; Goldey et al, 1995; Kuriyama & Chahoud, 2004; Allen et al, 1976; Levin et al, 1988), all indicating neurobehavioral deficits. Lilienthal & Winneke (1991) used a cross-fostering study design to demonstrate that prenatal rather than postnatal exposure to PCBs was responsible for neurobehavioral deficits in rodents.…”