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INHIBITION OF NEURAL CREST CELL MIGRATION BY THE WATER DISINFECTION BYPRODUCTS DICHLORO-, DIBROMO-, AND BROMOCHLORO-ACETIC ACID.
Citation:
Andrews, J E., H P. Nichols, J E. Schmid, AND E S. Hunter III. INHIBITION OF NEURAL CREST CELL MIGRATION BY THE WATER DISINFECTION BYPRODUCTS DICHLORO-, DIBROMO-, AND BROMOCHLORO-ACETIC ACID. Presented at Society of Toxicology, San Francisco, CA, March 25 - 29, 2001.
Description:
INHIBITION OF NEURAL CREST CELL MIGRATION BY THE WATER DISINFECTION BYPRODUCTS DICHLORO-, DIBROMO- AND BROMOCHLORO-ACETIC ACID. JE Andrews, H Nichols, J Schmid 1, and ES Hunter. Reproductive Toxicology Division, 1Research Support Division, NHEERL, USEPA, RTP, NC, USA.
The chlorination of drinking water results in production of numerous disinfection by-products (DBPs). One of the important classes of DBPs is the haloacetic acids. We have previously shown developmental toxicity of three haloacetic acids (HAs) dichloro- (DCA), dibromo-(DBA) and bromochloro- (BCA)acetic acid both individually and in combination in whole rat embryo culture (WEC) . The observed pattern of anomalies (prosencephalic, visceral arch, heart and eye defects) suggested that certain of the HAs may be affecting neural crest cell function. This study explores the question of effects on neural crest cell or somitic cell populations following exposure of cultures to HAs. Gestational day (GD) 9.5 rat embryo neural crest cell (NC) explants or GD 11.5 rat embryo somitic tissue were cultured for 24 hours and then exposed to HBSS or various concentrations (concentrations which were found to not be significantly lethal previously in WEC) of the three HAs for an additional 24 hours. The somitic cells migrated in multiple cell layers whereas the NC cells migrated in a monolayer. Photographs were taken of the cell cultures at the end of 24 and 48 hour periods and then evaluated for differential cell migration and morphology. NC and somitic cells grew radially from explants throughout the 48 hour period. Somitic cell migration was not significantly affected by exposure to any of the three HAs at concentrations which were previously found to be dysmorphogenic in WEC. BCA exposure resulted in a concentration dependent inhibition of NC cell migration. Exposure to the highest concentration of BCA (300 ?M) resulted in a 50% inhibition of NC cell migration. DBA at 342 ?M gave approximately 15% inhibition and DCA at 2500 ?M did not inhibit NC cell migration significantly. The percent NC cell inhibition BCA>DBA>>DCA is in agreement with the dysmorphology and %anomalies seen in WEC at these concentrations and suggests a selective sensitivity of the NC cells to BCA and DBA. (This abstract does not reflect US EPA policy)