The degree of PCB chlorination determines whether the rise in urinary homovanillic acid production in rats is peripheral or central in origin

Seegal, Richard F.; Brosch, Karl O.; Okoniewski, Richard

doi:10.1016/0041-008x(88)90015-4

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…In a similar study, there was a dose -dependent decrease in the levels of dopamine in the caudate nucleus, but not in the lateral olfactory tract, of adult rats exposed to 500 or 1000 mg / kg of a mixture of Aroclors 1254 and 1260 ( Seegal et al, 1986b ). In a subsequent study, a dose of 1000 mg / kg of Aroclor 1016 increased dopamine turnover in peripheral neurons of rats, whereas the same dose of an Aroclor 1254 /1260 mixture increased dopamine turnover in central neurons ( Seegal et al, 1988 ), suggesting that PCBs with different degrees of chlorination can alter dopaminergic functions in different locations of the nervous system. Treatment of adult male rats with a diet that provided approximately 0, 39, or 79 mg /kg /day Aroclor 1254 for 30 days resulted in significant decreases in dopamine concentrations and metabolism in the striatum and the lateral olfactory tract, but not in other brain areas (Seegal et al, 1991a ).…”

Section: Oral Exposurementioning

confidence: 98%

Effects of polychlorinated biphenyls on the nervous system

2000

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The neurological effects of polychlorinated biphenyls (PCBs) have been extensively investigated in humans and in animals. The main focus in human studies has been on the effects in neonates and young children, although studies of adults have also been conducted. A great deal of concern exists that even low levels of PCBs transferred to the fetus across the placenta may induce long-lasting neurological damage. Because PCBs are lipophilic substances, there is also concem that significant amounts might be transferred to nursing infants via breast milk. Studies in humans who consumed large amounts of Great Lakes fish contaminated with environmentally persistent chemicals, including PCBs. have provided evidence that PCBs are important contributors to subtle neurobehavioral alterations observed in newborn children and that some of these alterations persist during childhood. Some consistent observations at birth have been motor immaturity and hyporeflexia and lower psychomotor scores between 6 months and 2 years old. There is preliminary evidence that highly chlorinated PCB congeners, which accumulate in certain fish, are associated with neurobehavioral alterations seen in some newbom children. Subtle neurobehavioral alterations have also been observed in children bom to mothers in the general population with the highest PCB body burdens. Because of the limitations of epidemiological studies, these effects cannot be attributed entirely to PCB exposure. In one general population study, there was strong evidence that dioxins, as well as PCBs, were contributors to the neurobehavioral effects seen in exposed children. Children born to women who accidentally consumed rice oil contaminated with relatively high amounts of PCBs and chlorinated dibenzofurans (CDFs) during pregnancy also had neurodevelopmental changes. Studies in animals support the human data. Neurobehavioral alterations have been also observed in rats and monkeys following prenatal and/or postnatal exposure to commercial Aroclor mixtures, defined experimental congener mixtures, single PCB congeners, and Great Lakes contaminated fish. In addition, monkeys exposed postnatally to PCB mixtures of congeneric composition and concentration similar to that found in human breast milk showed learning deficits long after exposure had ceased. A few other generalizations can be made from the data in animals. It appears that ortho-substituted PCB congeners are more active than coplanar PCBs in modifying cognitive processes. In addition, one effect observed in both rats and monkeys--deficits on delayed spatial alternation--has been known to be induced by exposure to ortho-substituted PCBs, defined experimental mixtures, and commercial Aroclors. Both dioxin-like and non-dioxin-like PCB congeners have been shown to induce neurobehavioral alterations in animals. Changes in levels of neurotransmitters in various brain areas have also been observed in monkeys, rats, and mice. Of all the observed changes, the most consistent has been a decrease in dopamine content in basal ganglia ...

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Section: Oral Exposurementioning

confidence: 98%

Effects of polychlorinated biphenyls on the nervous system

2000

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“…In our experiments, Aroclor 1254 is the only mixture that contains significant amounts of dioxin-like PCBs (Aroclor 1016 contains trace amounts of DL congeners but has a Dioxin TEQ of 0.09 compared to a TEQ of 21 for Aroclor 1254) . Aroclor 1254 has also been shown to lead to higher levels of DNA damage, tumorigenesis, and disruption of central nervous system neurochemical function than Aroclor 1016. ,, This disruption may be due to dose-dependent inhibition of creatine kinase activity as seen in L6 myoblasts . Creatine kinase-B activity is decreased in adipocytes during obesity, thus opening the potential for a mechanistic tie between Aroclor 1254 exposure and adipocyte dysfunction .…”

Section: Implications For Human Healthmentioning

confidence: 68%

“… 65 Aroclor 1254 has also been shown to lead to higher levels of DNA damage, tumorigenesis, and disruption of central nervous system neurochemical function than Aroclor 1016. 3 , 66 , 67 This disruption may be due to dose-dependent inhibition of creatine kinase activity as seen in L6 myoblasts. 68 Creatine kinase-B activity is decreased in adipocytes during obesity, thus opening the potential for a mechanistic tie between Aroclor 1254 exposure and adipocyte dysfunction.…”

Section: Implications For Human Healthmentioning

confidence: 99%

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl

Behan-Bush

Liszewski

Schrodt

et al. 2023

Environ. Sci. Technol.

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Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 μM, the majority of MSCs die, while at 1−10 μM, MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, the MSC rate of expansion slowed and morphology changed. Further assessment revealed that PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs' role in supporting the growth and maintenance of adipose tissue.

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“…Aroclor 1254 has also been shown to lead to higher levels of DNA damage, tumorigenesis, and disruption of central nervous system neurochemical function than Aroclor 1016. 3,58,59 This disruption may be due to a dose-dependent inhibition of creatine kinase activity as seen in L6 myoblasts. 60 Creatine kinase-B activity is decreased in adipocytes during obesity, thus opening the potential for a mechanistic tie between Aroclor 1254 exposure and adipocyte disfunction.…”

Section: Implications For Human Healthmentioning

confidence: 99%

Toxicity impacts on human adipose MSCs acutely exposed to Aroclor and non-Aroclor mixtures of PCBs

Behan-Bush

Liszewski

Schrodt

et al. 2022

Preprint

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PCBs accumulate in adipose where they may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 μM, the majority of MSCs die, while at 1-10 μM MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, MSC rate of expansion slowed, and morphology changed. Further assessment revealed PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs role in supporting the growth and maintenance of adipose tissue.

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The degree of PCB chlorination determines whether the rise in urinary homovanillic acid production in rats is peripheral or central in origin

Cited by 8 publications

References 11 publications

Effects of polychlorinated biphenyls on the nervous system

Effects of polychlorinated biphenyls on the nervous system

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl

Toxicity impacts on human adipose MSCs acutely exposed to Aroclor and non-Aroclor mixtures of PCBs

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