Molecular mechanisms involved in the toxic effects of polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs).
Exposure to polychlorinated biphenyls (PCBs) and brominated flame-retardants (BFRs) in human, primates, and rodents is accompanied by neurobehavioral changes. These involve adverse effects on both memory and learning and motor activity. There are also adverse effects observed on the endocrine and immune system. This review is restricted to our laboratory's recent findings of effects of these compounds on the nervous system and some molecular effects on the immune system. In the nervous system, data showed that PCBs and BFRs produce an effect on neurotransmitter transport mechanisms, in particular the neurotransmitter dopamine. It was demonstrated that this might explain the loss of dopamine in the brain seen after exposure to PCB. Further, it may explain the behavior of dopamine in preparations in vitro from brain tissue after exposure to PCB. Recently it was also reported that PCB and some BFRs induce formation of reactive oxygen species (ROS) in neurons. ROS act as messengers in the nervous system and may also be involved in cell death. In the case of PCB exposure, a correlation between ROS formation and death of neurons was found. In the immune system it was shown that PCBs and some of the BFRs induce formation of ROS in neutrophils (granulocytes). This takes place primarily through phosphorylation and subsequent activation of the NADPH oxidase. This production of ROS may have an adverse effect on the immune system.
Fonnum
F
F
Group of Molecular Neurobiology, Institute of Basal medicine, University of Oslo, Oslo, Norway. frode.fonnum@bio.uio.no
Mariussen
E
E
Reistad
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005411:Flame Retardants / Q000633:toxicity*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010647:Phenyl Ethers / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D017382:Reactive Oxygen Species; D011078:Polychlorinated Biphenyls; D002118:Calcium