title: Polychlorinated biphenyls and polybrominated diphenyl ethers alter striatal dopamine neurochemistry in synaptosomes from developing rats in an additive manner.
abstract: Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are widespread environmental contaminants associated with changes in behavior and neurochemical function in laboratory animals and behavioral deficits in children. PCBs and PBDEs are found in food, especially in seafood and dairy products, and coexposure to these contaminants is likely. We examined the effects of an environmentally relevant mixture of PCBs (Fox River Mix [FRM]) and a PBDE mixture (DE-71) alone and in combination on synaptosomal and medium dopamine (DA) levels and the levels of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in striatal synaptosomes derived from postnatal days (PND) 7, PND14, or PND21 rats. FRM elevated medium DA and reduced synaptosomal DA concentrations with greater potency than equimolar concentrations of DE-71. The effects of FRM, but not DE-71, were dependent on the age of the animals from which the synaptosomes were derived, with greater effects observed in synaptosomes from the youngest animals. We used Bliss' model of independence to assess the possible interaction(s) of a 1:1 mixture of FRM and DE-71 on synaptosomal DA function and found that the effects of the FRM/DE-71 mixture were additive. Furthermore, as for FRM alone, the effects of the FRM/DE71 mixture were greater in synaptosomes prepared from PND7 rats than in synaptosomes from PND14 and PND21 rats. Because the effects of these contaminants are additive, it is necessary to take into account the cumulative exposure to organohalogen contaminants such as PCBs and PBDEs during risk assessment.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA. axd17@health.state.ny.us
authors.forename: Anne
authors.initials: A
authors.lastname: Dreiem
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Okoniewski
authors.forename: Karl O
authors.initials: KO
authors.lastname: Brosch
authors.forename: Veronica M
authors.initials: VM
authors.lastname: Miller
authors.forename: Richard F
authors.initials: RF
authors.lastname: Seegal
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000633:toxicity*; D005411:Flame Retardants / Q000633:toxicity; D005506:Food Contamination; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D018570:Risk Assessment; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D015102:3,4-Dihydroxyphenylacetic Acid; C086401:pentabromodiphenyl ether; D011078:Polychlorinated Biphenyls; D004298:Dopamine