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Title: Multiple mechanisms of PCB neurotoxicity

Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humansmore » exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.« less
Authors:
; ;  [1]
  1. Univ. of New York, Albany, NY (United States) [and others
Publication Date:
OSTI Identifier:
567728
Report Number(s):
CONF-9611157--
ON: DE97009015; TRN: 98:000722-0031
Resource Type:
Conference
Resource Relation:
Conference: 1996 Pacific Basin conference on hazardous waste, Kuala Lumpur (Malaysia), 4-8 Nov 1996; Other Information: PBD: [1996]; Related Information: Is Part Of Pacific Basin conference on hazardous waste: Proceedings; PB: 706 p.
Research Org:
Argonne National Lab., IL (United States)
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; POLYCHLORINATED BIPHENYLS; NERVOUS SYSTEM; TOXICITY; PRENATAL EXPOSURE; HEALTH HAZARDS