Polychlorinated Biphenyls Mixture Research Articles

Differential in vitro neurotoxicity of the flame retardant PBDE-99 and of the PCB Aroclor 1254 in human astrocytoma cells

Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because of their presence in maternal milk and their structural similarity to polychlorinated biphenyls (PCBs), concern has been raised on their possible developmental neurotoxicity. Aim of the present study was to investigate the in vitro effects of PBDE-99 (2,2′, 4,4′, 5-pentabromodiphenyl ether) on astroglial cells (human 132-1N1 astrocytoma cells) and comparing it with those of the PCB mixture Aroclor 1254. Both PBDE-99 and Aroclor 1254 caused a concentration-dependent inhibition of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, however, only the latter increased lactate dehydrogenase (LDH) release or cell death, assessed by the trypan blue assay. PBDE-99 caused translocation of the three protein kinase C (PKC) isozymes (α, ɛ, ζ) present in 132-1N1 astrocytoma cells, while Aroclor 1254 affected only PKCα and ɛ translocation. However, pre-incubation with the PKC inhibitor GF109203X or PKC down-regulation by the phorbol ester PMA, had minimal or no effect on PBDE-99 or Aroclor 1254-induced cytotoxicity. Similarly, the calcium chelator BAPTA-AM, the tyrosine kinase inhibitor genistein, and the MEK (mitogen activated protein kinase kinase) inhibitor PD98059 had no effect on PBDE-99 and Aroclor 1254 cytoxicity. On the other hand, the phosphatidylinositol 3 kinase (PI-3K) inhibitor LY290042 enhanced PBDE-99 toxicity, but did not affect Aroclor 1254. Because of the involvement of PI-3K in apoptotic cell death, the ability of PBDE-99 and Aroclor 1254 to induce apoptosis in astrocytoma cells was investigated. PBDE-99, but not Aroclor 1254, caused apoptotic cell death in astrocytoma cells, assessed by the TUNEL method and by Hoechst 33258 staining, via a p53 dependent mechanism. These results suggest that PBDE-99 and Aroclor 1254 exert differential cytotoxic effects on human astroglial cells.

Ligninolytic fungi in bioremediation: extracellular enzyme production and degradation rate

Ligninolytic fungi can be used for remediation of pollutants in water and soil. Extracellular peroxidases and laccases have been shown to oxidize recalcitrant compounds in vitro but the likely significance of individual enzyme levels in vivo remains unclear. This study documents the amounts and activities of Mn-dependent peroxidase (MnP), lignin peroxidase and laccase (LAC) in various species of ligninolytic fungi grown in liquid medium and soil and their effect on degradation of polycyclic aromatic hydrocarbons (anthracene and pyrene), a polychlorinated biphenyl mixture (Delor 106) and a number of synthetic dyes. Stationary cultures of a highly degradative strain Irpex lacteus exhibited 380-fold and 2-fold increase in production of MnP and LAC, respectively, compared to submerged cultures. Addition of Tween 80 to the submerged culture increased MnP levels 260-fold. High levels of MnP correlated with efficient decolorization of Reactive Orange 16 azo dye but not of Remazol Brilliant Blue R anthraquinone dye. Degradation of anthracene and pyrene in spiked soil by straw-grown explorative mycelium of Phanerochaete chrysosporium, Trametes versicolor and Pleurotus ostreatus showed the importance of MnP and LAC levels secreted into the soil. The importance of high fungal enzyme levels for efficient degradation of recalcitrant compounds was better demonstrated in liquid media compared to the same strains growing in soil.

The inhibition of LPS-induced splenocyte proliferation by ortho-substituted and microbially dechlorinated polychlorinated biphenyls is associated with a decreased expression of cyclin D2.

Immunological effects of polychlorinated biphenyls (PCBs) have been demonstrated in our laboratories with the peferential inhibition of lipopolysaccharide (LPS)-induced splenocyte proliferation by ortho-substituted PCB congeners. An investigation of the mechanism behind this immunotoxicity revealed an interruption in the progression of murine lymphocytes from G0/G1 into S phase by Aroclor 1242 and the di-ortho-substituted congener, 2,2'-chlorobiphenyl (CB), whereas, a non-ortho-substituted congener, 4,4'-CB, did not affect cell cycle progression. This interruption of cell cycle progression by 2,2'-CB and Aroclor 1242 was associated with a decreased expression of the cell cycle regulatory protein, cyclin D2, while expression was not affected by exposure to the non-ortho-substituted 4,4'-CB. These results suggest the preferential inhibition of LPS-induced splenocyte proliferation by ortho-substituted congeners is a result of a decreased expression of cyclin D2, which leads to an interruption in cell cycle progression. In addition, PCB mixtures with an increased percentage of chlorines in the ortho position following an environmentally occurring degradation process inhibited LPS-induced proliferation, interrupted cell cycle progression, and decreased cyclin D2 expression. This study provides evidence for a mechanism of action of the immunological effects of ortho-substituted individual congeners as well as environmentally relevant mixtures enriched in congeners with this substitution pattern.

Hippocampal Long-Term Potentiation (LTP) is Reduced by a Coplanar PCB Congener

Neurotoxicity of polychlorinated biphenyls (PCBs) is usually ascribed to the ortho-substituted congeners. We have examined the effects of acute perfusion of 3,3′,4,4′-tetrachlorobiphenyl (PCB 77), a coplanar, dioxin-like congener, on long-term potentiation (LTP) in the Schaffer collateral-CA1 and the mossy fiber-CA3 pathways in mouse hippocampus. LTP in both pathways was blocked by PCB 77, with a threshold effect at a concentration of 1 μM. LTP is a useful model of learning and memory function in which a patterned stimulation of an afferent pathway produces a persistent increase in the efficacy of synaptic transmission. LTP is reduced by PCB mixtures and ortho-substituted congeners at concentrations comparable to those studied here. These observations provide evidence in support of the hypothesis that dioxin-like and non-dioxin-like PCB congeners are equally potent in causing the cognitive decrements seen in children exposed prenatally to PCBs.

Estrogenic and toxic effects of polychlorinated biphenyls on cultured ovarian germ cells of embryonic chickens

Polychlorinated biphenyls (PCBs) are man-made ubiquitous pollutants that have detrimental effects on reproduction and endocrine functions in a variety of species. In the present study, estrogenic and toxic effects of PCBs on embryonic chicken ovarian development were evaluated by a germ-somatic cell co-culture system. Ovarian cells were cultured in serum-free medium and challenged with a mixture of PCBs (Aroclor 1254). Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release. Results showed that lower PCBs (0.1–1 μg/ml) manifested mainly estrogenic effect to stimulate germ cell proliferation, while higher PCBs (10 μg/ml) imposed severe toxicity on germ and somatic cells. The toxic effect of PCBs could be attenuated by an antioxidant tocopherol. PCBs induced condensed nuclear chromosome in ovarian cells and caused cell exfoliation and breakdown within initial hours of treatment. After 24 h, the estrogenic effect of PCBs began to exhibit and the survived germ cells manifested proliferation. Inhibition of the estrogenic effect of PCBs by tamoxifen led to increased toxicity on germ cells and somatic cells. These results indicate that PCBs exposure may interfere with ovarian germ cell proliferation and cause reproductive disorder via both toxic and estrogenic actions in embryonic chickens.

Polychlorinated Biphenyl Mixture Aroclor 1254-Induced Oxidative Stress Plays a Role in Dopaminergic Cell Injury

Oxidative stress (OS) is thought to participate in the pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Excessive reactive oxygen species (ROS) production can occur during the normal aging process or following exposure to environmental toxicants. Dopamine neurons, which degenerate during PD, are particularly sensitive to oxidative stress. Polychlorinated biphenyls (PCBs), persistent and widespread pollutants, have been shown to adversely impact dopaminergic (DAergic) pathways, but the role ROS play in neurotoxicity remains unclear. To test the hypothesis that PCB exposure compromises dopamine neurons by stimulating ROS production, the direct toxicity and oxidative stress response following PCB exposure was examined both in MN9D dopamine cells and primary mesencephalic cultures. PCBs induced a time- and concentration-dependent increase in ROS production, which preceded cytotoxicity. Whereas intracellular GSH depletion exacerbated PCB effects, antioxidant pretreatment attenuated ROS production and cell death. Coincident alterations in antioxidant defense enzymes also accompanied ROS production, including decreased MnSOD and increased CuZnSOD protein levels. The robust elevation in heme oxygenase-1 levels further support the activation of oxidative stress mechanisms following PCB exposure. Furthermore, PCBs produced concentration-dependent reductions in intracellular dopamine levels and elevated dopamine turnover. Although the intracellular source of ROS remains unknown, these results suggest that sublethal PCB concentrations activate an oxidative stress-related pathway, which potentially disrupts dopamine neuron function.

Influence of a combination of two tetrachlorobiphenyl congeners (PCB 47; PCB 77) on thyroid status, choline acetyltransferase (ChAT) activity, and short- and long-term memory in 30-day-old Sprague-Dawley rats.

The important role of thyroid hormones in growth and development, maintenance of body temperature, digestion, cardiac function, and normal brain development can be disrupted by environmental contaminants like polychlorinated biphenyls (PCB). Polychlorinated biphenyls are environmental contaminants that are widespread, persistent, lipophilic, and bioaccumulate through food webs, concentrating in adipose tissue. Placental and lactational PCB exposure of offspring causes metabolic and endocrine disruptions including hypothyroxinemia, spatial learning and memory deficits, neurochemical and neurobehavioral alterations, and reproductive problems. Previous studies in our lab using the individual congeners PCB 47 (2,2',4,4'-tetrachlorobiphenyl, ortho-substituted) and PCB 77 (3,3',4,4'-tetrachlorobiphenyl, non-ortho-substituted) have demonstrated alterations in thyroid hormone levels, alterations in brain choline acetyltransferase (ChAT) activity, and spatial learning deficits. In the present study, pregnant Sprague-Dawley rats were fed a diet with or without a mixture of PCB 47/77 at 1.25 ppm, 12.5 ppm or 25.0 ppm (w/w). Rat pups were swum in the Morris water maze four times a day on days 21-29 in order for the animals to learn the position of a submerged fixed platform. A probe test was run on day 24 (30 min after last swim) for short-term memory, and on day 29 (24 h after the last swim) for long-term memory after removal of the platform. Time spent in the quadrant previously containing the platform was recorded. Rats were decapitated on day 30, serum collected and frozen at -20 degrees. ChAT activity was measured radiometrically in basal forebrain and hippocampus. All PCB-treated animals experienced a depression in both triiodothyronine (T3) and thyroxine (T4). The present study found that all doses of PCB depressed ChAT activity in hippocampus with no significant alteration in the basal forebrain. In PCB-treated animals, short-term memory showed a trend toward improvement and long-term memory toward depression, but these trends were not significant. The consequences likely stem from endocrine disruption, especially with regard to the thyroid.

Dietary exposure to Aroclor 1254 alters gene expression in Xenopus laevis frogs

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that contribute to worldwide health problems. Despite data associating PCBs with adverse health effects, decisions to clean up contaminated sites remain controversial. Cleanup decisions are typically based on risk assessment methods that are not sensitive enough to detect subtle changes in health. We have recently shown that gene expression signatures can serve as sensitive molecular biomarkers of exposure and related health effects. Our initial studies were carried out with developing Xenopus laevis tadpoles that were exposed to the PCB mixture Aroclor 1254 (A1254) for 2 days. A1254 was dissolved in dimethyl sulfoxide and added to the aquarium water for rapid loading of PCBs into the tadpole tissue. These studies showed that increases in the expression of specific genes occurred independent of adverse health effects, and decreases in specific genes correlated with the appearance of observable health effects, including decreased survival and gross morphological and behavioral abnormalities. In this report, we extend our previous work to test the use of gene expression signatures as biomarkers in frogs exposed to PCBs through the diet from early tadpole stages through metamorphosis. This work showed that chronic low-dose exposure to A1254 (24ppm) in food produced tissue levels of 17ppm and increased gene expression of nerve growth factor and proopiomelanocortin independent of adverse health effects. Exposure to higher doses of A1254 (200ppm) produced tissue levels of 80ppm and increased expression of p450 1A1, also, independent of adverse health effects. This work provides further evidence for the use of gene expression changes as biomarkers of exposure to PCBs.

Development and characterization of new monoclonal antibodies specific for coplanar polychlorinated biphenyls

Three polychlorinated biphenyls (PCBs) widely recognized as being among the most toxic, 3,3′,4,4′-tetrachlorobiphenyl (PCB77), 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) and 3,3′,4,4′,5,5′ -hexachlorobiphenyl (PCB169) were each chemically substituted at the para position and attached to BSA via carboxylic acid spacers by the N-hydroxysuccinimide active ester method. The three resultant immunogens were used to stimulate immune responses in mice. Three of the resultant monoclonal antibodies were selected on the basis of target recognition and dimethyl sulfoxide tolerance and taken forward for further study and affinity measurement using a flow based immunoassay platform. The high sensitivity of the immunoassay platform used allows use of antibody concentrations below the K d (=1/affinity) of the antibody offering ideal conditions to achieve K d limited detection, the theoretical limit for the antibody used. One of the three antibodies exhibits high affinity binding to all three of the target PCBs, showing dynamic ranges in 2% (v/v) dimethyl sulfoxide of approximately 200 ng l −1 to 14 μg l −1 for PCB77, 160 ng l −1 to 6 μg l −1 for PCB126 and 22 ng l −1 to 1.4 μg l −1 for PCB169. In addition, this antibody showed low cross reactivity to a panel of structurally similar PCBs, and to four common commercial mixtures of PCBs, Kanechlor 300, 400, 500 and 600. Data are included showing that the detection limit for PCB169 is not affected by the presence of a 50-fold excess of commercial PCB mixture Kanechlor 300.

Inhibition of aroclor 1254-induced depletion of stored calcium prevents the cell death in catecholaminergic cells.

The relationship between depleting effects of polychlorinated biphenyls (PCBs) on the intracellular calcium store and PCBs-induced cell death in dopaminergic cells has not been fully evaluated. Here, we evaluated the effects of inhibitors of the release of ER-stored calcium on the cytotoxicities induced by 10 microg/ml of Aroclor 1254 (A1254; polychlorinated biphenyl mixture) in a catecholaminergic cell-line, CATH.a cells. Exposure to A1254 produced an elevation in free calcium ([Ca2+]i) in the presence or absence of extracellular calcium and decreased in cell viability. From our results, we deduced that the A1254-induced elevation of [Ca2+]i resulted from the depletion of ER-stored calcium. The [Ca2+)]i elevation was dramatically inhibited by an inositol 1,4,5-triphosphate receptor (IP3R) antagonist, and slightly inhibited by a ryanodine receptor (RyR) blocker. IP3R blockers conferred significant protection against A1254-induced cell death, as did RyR blockers, but calcium chelators or NMDA blockers did not. However, none of these reagents inhibited the depletion of intracellular dopamine by A1254 indicating that the mechanism of PCB-induced dopamine depletion may be independent of calcium alterations. Taken together, these data suggest that agents inhibiting the receptor-mediated depletion of stored calcium can prevent the A1254-induced cell death, but not modulate the A1254-induced intracellular dopamine depletion in CATH.a cells.

Suppression of aromatase activity in vitro by PCBs 28 and 105 and Aroclor 1221

The effects of polychlorinated biphenyls (PCBs) on human cytochrome P450 aromatase activity in vitro were investigated using a commercially available microsomal fraction obtained from baculovirus infected insects that had been transfected with the human CYP19 gene and cytochrome P450 reductase. The assay measured the conversion of tritiated testosterone to estradiol in Tris buffer at pH 7.4. When aroclors, commercial preparations of PCBs, were added to aromatase assays at a 10 μM concentration, Aroclor 1221 caused a reduction in the aromatase activity, whereas other aroclors (1016, 1232, 1242, 1248, 1254, 1260, 5432, 5442 and 5460) were without effect. Further investigation of the effect of Aroclor 1221 on aromatase activity showed that the inhibition was dose dependent. When a reconstituted mixture (RM) of PCBs that represented the congeneric content of human milk was investigated, no inhibition of aromatase activity at the maximum treatment of 15.0 μM was observed. None of the congeners present in the reconstituted mixture, except PCB 28 and 105, affected P450 arom activity. PCB 28 showed a statistically significant inhibition of aromatase activity ( P<0.05) at 1.5 and 15 μM and a significant inhibition of aromatase activity by PCB 105 was also observed, but only at 15 μM. In three separate kinetic analyses the K m(app) for aromatase was 64, 89 and 69 nM (mean 74 nM). In addition, PCB 28 resulted in an increase in the K m(app) without a significant effect on V max(app), suggesting competitive inhibition by this congener. This conclusion was supported by slope ( K m(app)/ V max(app) versus [inhibitor]) and intercept (1/ V max(app) versus [inhibitor]) replots. The slope replots gave K i(app) values for PCB 28 of 0.9, 1.3 and 2.0 μM (mean 1.4 μM), whereas intercept replots were almost horizontal. Thus, PCB 28 is a competitive inhibitor of aromatase with a K i(app) value approximately 20-fold the K m(app) value. Based on these studies, we conclude that most PCBs are not inhibitors of aromatase activity in vitro. However, as being inhibitors of aromatase activity, Aroclor 1221, PCB 28 and PCB 105 would remain a priority for further study as possible endocrine disrupters.

Inhibition of aroclor 1254-induced depletion of stored calcium prevents the cell death in catecholaminergic cells

The relationship between depleting effects of polychlorinated biphenyls (PCBs) on the intracellular calcium store and PCBs-induced cell death in dopaminergic cells has not been fully evaluated. Here, we evaluated the effects of inhibitors of the release of ER-stored calcium on the cytotoxicities induced by 10 μg/ml of Aroclor 1254 (A1254; polychlorinated biphenyl mixture) in a catecholaminergic cell-line, CATH.a cells. Exposure to A1254 produced an elevation in free calcium ([Ca2+]i) in the presence or absence of extracellular calcium and decreased in cell viability. From our results, we deduced that the A1254-induced elevation of [Ca2+]i resulted from the depletion of ER-stored calcium. The [Ca2+]i elevation was dramatically inhibited by an inositol 1,4,5-triphosphate receptor (IP3R) antagonist, and slightly inhibited by a ryanodine receptor (RyR) blocker. IP3R blockers conferred significant protection against A1254-induced cell death, as did RyR blockers, but calcium chelators or NMDA blockers did not. However, none of these reagents inhibited the depletion of intracellular dopamine by A1254 indicating that the mechanism of PCB-induced dopamine depletion may be independent of calcium alterations. Taken together, these data suggest that agents inhibiting the receptor-mediated depletion of stored calcium can prevent the A1254-induced cell death, but not modulate the A1254-induced intracellular dopamine depletion in CATH.a cells.

Developmental toxicity of polychlorinated biphenyls (PCBs): a systematic review of experimental data.

Experimental reproductive and developmental toxicity studies with polychlorinated biphenyls (PCBs) are reviewed in brief to determine their relevance for current environmental exposure of humans during the prenatal and postnatal developmental periods. Additional material is published in electronic form only, which contains graphic overviews on individual PCBs and various mixtures that are linked with the relevant citations. In this comprehensive article we focus on interactions of PCBs with biological substrates that could mediate adverse effects observed in experimental animals and in children, and the shortcomings of many of the animal studies available. A main point of criticism involves the relative lack of animal data on several of those persistent congeners, either as individual compounds or as environmentally relevant mixtures, which are currently used as a measure of human exposure. Experimental studies in animals are frequently conducted with commercial PCB mixtures, a test design that does not reflect the exposure situation in humans. Important improvements of animal experiments could be achieved by more complete reporting of litter data (pre- and post-natal losses, toxic signs in the dam and the offspring, birth weights and postnatal growth data), the inclusion of endpoints that have been found previously to be affected by PCBs, and measurements of internal exposure data.

Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants routinely found in human and animal tissues. Developmental exposure to PCBs is associated with neuropsychologic deficits, which may be related to effects on thyroid hormone (TH) signaling in the developing brain. However, PCBs may interfere with TH signaling solely by reducing circulating levels of TH, or they may exert direct effects on TH receptors (TRs). Therefore, we tested whether maternal exposure to a commercial PCB mixture, Aroclor 1254 (A1254), exerts effects in the fetal brain by one or both of these mechanisms. Dams were dosed daily with 0, 1, or 4 mg/kg A1254 from gestational day 6 (GD6) until they were sacrificed on GD16. A1254 significantly reduced circulating levels of triiodothyronine (T3) and thyroxine (T4) in pregnant rats but increased the expression of several TH-responsive genes in the fetal cortex, including neuroendocrine-specific protein A (NSP-A), RC3/neurogranin, and Oct-1. These findings are consistent with a direct action of PCBs on TRs. However, we did not identify parent PCB congeners or metabolites that bound to rat TRs isolated from hepatic nuclei. These findings indicate that PCBs can interfere with TH signaling in the fetal brain by direct actions on the fetus rather than by producing maternal hypothyroidism.

PCB-induced inhibition of the vesicular monoamine transporter predicts reductions in synaptosomal dopamine content.

Both Aroclor mixtures and individual non-coplanar polychlorinated biphenyl (PCB) congeners reduce dopamine (DA) concentrations in cells in culture and in the brains of developing and adult laboratory animals. These reductions may involve inhibition of the dopamine transporter (DAT) and the vesicular monoamine transporter (VMAT) responsible, respectively, for the uptake of extracellular DA and the packaging of nerve terminal cytosolic DA into synaptic vesicles. However, the relative contribution of each monoamine transporter to the PCB-induced reductions in tissue DA has not been determined. Accordingly, we exposed striatal synaptosomes from adult rats to individual PCB congeners, a commercial mixture of PCBs or known monoamine transporter inhibitors; measured synaptosomal DA; and related these changes to media DA and concentrations of 3,4-dihydroxyphenylacetic (DOPAC). PCB-induced elevations in media DA concentrations are not sufficient to explain the reductions in tissue DA because known DAT inhibitors elevate media DA to a much greater extent than PCBs and yet induce similar decreases in tissue DA concentrations. On the other hand, PCB-induced elevations in DOPAC, reflective of increases in nerve terminal cytosolic DA, are sufficient to explain the reductions in tissue DA, because a known VMAT inhibitor elevates DOPAC and reduces tissue DA to an extent similar to that seen with PCBs. Taken together, these results suggest that elevations in DOPAC, reflective of increases in nerve terminal cytosolic DA due to VMAT inhibition, rather than elevations in media DA due to DAT inhibition, are largely responsible for the observed decreases in tissue DA content.

Aroclor 1254 inhibits tryptophan hydroxylase activity in rat brain.

Previous studies have shown that oral exposure of rats to polychlorinated biphenyls (PCBs) results in reduced 5-hydroxytryptamine (5-HT) concentrations in certain brain regions. In the present study, we investigated whether the PCB mixture Aroclor 1254 (0.33 mg/g body weight as a single oral dose) can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis, and reduce 5-HT concentrations in selected brain areas. In two separate experiments, Aroclor 1254 exposure consistently reduced TPH activity in the brainstem (7.2 and 8.7%), frontal cortex (17.4 and 14.8%), and hypothalamus (10.7 and 9.4%) without altering the rats' food intake or growth. Moreover, Aroclor 1254 accumulation in the frontal cortex demonstrated a negative correlation with TPH activity (correlation coefficient -0.82). In addition, 5-HT concentrations decreased in the brainstem and frontal cortex after Aroclor 1254 exposure by 9.1 and 19.7%, respectively. These results suggest that the Aroclor 1254-induced decreases in 5-HT concentrations in certain areas of the rat brain are due to inhibition of TPH activity, similar to our recent observations in Atlantic croaker, and that TPH is one of the targets of PCB neurotoxicity in both fish and mammals.

Acute exposure to aroclor 1016 or 1260 differentially affects dopamine transporter and vesicular monoamine transporter 2 levels

Polychlorinated biphenyls (PCBs) have been shown to specifically target the dopaminergic nervous system, resulting in long-term reduction of striatal dopamine (DA) levels. However, the mechanism(s) by which PCBs exert this effect is not known. Here we report that decreased striatal dopamine levels are observed 1, 7, and 14 days after acute exposure to the common PCB mixtures Aroclor 1016 or 1260. Dopamine transporter (DAT) levels were decreased at all time points in Aroclor 1016 treated animals, and on Days 1 and 7 in Aroclor 1260 treated animals. Vesicular monoamine transporter 2 (VMAT2) levels were not affected by Aroclor 1016, but were significantly decreased 14 days after exposure to Aroclor 1260. Tyrosine hydroxylase expression, a marker of dopamine neuron integrity, was not significantly affected by PCB exposure at any time. These data suggest that PCB-induced reductions in striatal dopamine may be mediated by alterations in DAT and VMAT2 expression.

Research progress of the endocrine disrupting activities of polychlorinated biphenyls

Polychlorinated biphenyls (PCBs) are global persistent organic pollutants. Almost all commercial PCBs mixtures, single PCB congener, and their metabolites possess endocrine disrupting activities. They can disrupt the estrogen/androgen system, thyroid hormone system and other endocrine systems by interfering with the synthesis, transport, storage, metabolism, and feedback regulation of hormones. The newest data related to the endocrine disrupting activities of PCBs and their mechanisms are reviewed and the research perspectives are also discussed.

Fertilization success and sexual behavior in male medaka, Oryzias latipes, exposed to tributyltin

We evaluated the effects of tributyltin (TBT), polychlorinated biphenyls (PCBs), and a mixture of TBT and PCBs on reproduction, gonadal histology, and sexual behavior in Japanese medaka ( Oryzias latipes). We administered TBT (1 μg g −1 body weight [b.w.] daily), PCBs (1 μg g −1 b.w. daily), or both to medaka for 3 weeks. We assessed reproductive success during week 3 and the sexual behavior of male medaka after the exposure period. Fertilization success was significantly decreased in groups that received TBT. The profiles of fertility developed a bimodal distribution in the TBT and TBT + PCBs groups, and the numbers of males that performed “following” and “dancing” were significantly decreased in the TBT + PCBs group. The frequency of “dancing” also decreased after treatment with TBT, whereas fish that received PCBs only showed no difference in sexual behavior. Testes that had oocytes showed normal spermatogenesis, even though two of the five males treated with TBT + PCBs had some indication of testis–ova, which did not occur in any other group. Our results indicate that TBT, but not PCBs, affects sexual behavior and reproduction in medaka.

Early developmental neurotoxicity of a PCB/organochlorine mixture in rodents after gestational and lactational exposure.

The developmental and neurobehavioral effects of gestational and lactational exposure to a mixture of 14 polychlorinated biphenyls (PCBs) and 11 organochlorine pesticides was examined and compared against the commercial PCB mixture Aroclor 1254. The mixture was based on blood levels reported in Canadian populations living in the Great Lakes/St. Lawrence basin. Pregnant Sprague-Dawley rats were dosed orally with 0.013, 0.13, 1.3, or 13 mg/kg of the chemical mixture or 15 mg/kg of Aroclor 1254 from gestation day (GD) 1 to postnatal day (PND) 23. The highest mixture dose decreased maternal gestation and lactation body weight, and produced high mortality rates (80% overall) and reductions in offspring weight that persisted to adulthood. Aroclor 1254 produced smaller but persistent decreases in offspring weight without affecting maternal weight or offspring mortality. Aroclor 1254 and 13 mg/kg of the mixture produced comparable decreases in maternal and offspring serum T4 levels and comparable alterations to maternal thyroid morphology. Aroclor 1254 delayed the righting reflex and ear opening, accelerated eye opening, and reduced grip strength at PNDs 10-14. The mixture at 13 mg/kg delayed negative geotaxis in addition to delaying righting reflex and ear opening and reducing grip strength but had no effect on eye opening. Lower mixture doses (0.13 and 1.3 mg/kg) also delayed ear opening but affected no other parameters. Developmental exposure to the chemical mixture was found to be more toxic than exposure to Aroclor 1254 and produced a different profile of effects on early neurodevelopment. This PCB/organochlorine pesticide mixture affects mortality, growth, thyroid function, and neurobehavioral development in rodents.