W3 PM Biomarkers
Wednesday, 16 November 2005: 1:50 PM - 5:30 PM in Ballroom 3

(HEA-1117-727724) Does embryonic exposure to PCB 126 alter the CYP1A response to TCDD in cultured hepatocytes?

Head, J^{1, 2}, O'Brien, J³, Kennedy, S^{1, 2}, ¹ University of Ottawa, Ottawa, Ontario, Canada² National Wildlife Research Centre, Ottawa, Ontario, Canada³ Carleton University, Ottawa, Ontario, Canada

ABSTRACT- Concentrations of dioxin-like compounds in avian eggs can vary substantially between individuals, species, and collection sites. Although cytochrome p4501A (CYP1A) inducibility in hepatocyte cultures is commonly used to predict species sensitivity to environmental contaminants, it is not known how exposure to dioxin-like compounds during embryonic development might alter this biomarker response. To investigate this question, we injected vehicle, 0.4, 0.8, or 1.6 g/kg PCB 126 into the air cell of fertilized chicken eggs prior to incubation, and measured CYP1A endpoints in cultured hepatocytes of day 19 embryos from each treatment group. The most environmentally relevant treatment, 0.4 g/kg PCB 126, increased CYP1A4 expression 29-fold in whole liver, but only 2-fold in cultured hepatocytes. The CYP1A response to TCDD was not altered in hepatocytes cultured from 0.4 g/kg treated embryos, but at 0.8 and 1.6 g/kg PCB 126, several concentration-dependent effects were observed. For example, embryos exposed to higher concentrations of PCB 126 in ovo were more responsive to CYP1A mRNA induction by TCDD in vitro. EC50s were not affected by PCB 126 treatment. These findings suggest that exposure to environmental levels of dioxin-like compounds during incubation is not likely to alter species sensitivity estimates derived from in vitro CYP1A data.

Key words: biomarker, hepatocyte, CYP1A, dioxin