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ALTERED GENE EXPRESSION OF MOUSE EMBRYO CULTURES EXPOSED TO BROMOCHLOROACETIC ACID
Citation:
Karoly, E. D., J E. Schmid, AND E S. Hunter III. ALTERED GENE EXPRESSION OF MOUSE EMBRYO CULTURES EXPOSED TO BROMOCHLOROACETIC ACID. Presented at Teratology Society Meeting, Vancouver, British Columbia, Canada, June 26 - July 1, 2004.
Description:
An unintended consequence of chemical disinfection of municipal drinking water has been the production of disinfection by-products (DBPs) resulting from the interaction of chemical disinfectants and naturally occurring organic material present in the water. A major class of the DBPs are the haloacetic acids which are commonly found in disinfected water at concentrations higher than other DBPs. Bromochloroacetic acid (BCA), a DBP included within the family of haloacetic acids, is a reproductive toxicant in animal models. The mechanism of haloacetic acid embryotoxicity has not been defined, but may be mediated in part through the inhibition of protein kinases. In order to further examine the mechanism of BCA induced dysmorphogenesis CD-1 mouse embryos (3 to 6 somite stage) were cultured in 300?M BCA for 0, 1, 3 and 6h. Additionally, embryos were exposed to 30 and 3?M BCA for 6h. Following exposure, embryos were terminated and heads were collected for total RNA isolation. Total RNA was reverse transcribed with amino allyl-dUTP and indirectly labelled with Cy3 and Cy5. Fluorescently labelled cDNA from treated and untreated samples were labelled with Cy5 and hybridized against a Cy3 labelled whole embryo reference sample onto custom glass slide arrays. Arrays were spotted with 17,388 70mer oligonucleotide probes from the Operon Array-Ready Oligo Set for the mouse genome version 2. The data were normalized by slide using a Lowess normalization (SAS Proc Loess) with a smoothing parameter of 0.2. One-way ANOVA and regression analysis identified 1173 genes as being differentially expressed across dose or time. Cluster analysis and linear models were used to identify the transcriptional responses in mouse embryo culture exposed to BCA and their association with mouse embryotoxicity. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy. Funded by EPA/UNC Toxicology research program, training agreement CT 827206 with the Curriculum of Toxicology, University of North Carolina at Chapel Hill, North Carolina.