Research Project
2155761
Halogenated dioxins and related compounds are widespread environmental contaminants. Such "dioxin-like" compounds are typified by 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), 2,3-,4,7,8 pentachlorodibenzofuran (PCDF), and 3,3 ',4,4' ,5 pentachlorobiphenyl (PCB). These toxins have profound acute and chronic effects in birds and mammals, including humans. The toxic effects of compounds like TCDD are dependent on their ability to transform the Ah receptor. We have developed a simple in vitro bioassay for transformation of the Ah receptor. The assay is capable of detecting the presence of Ah transforming compounds such as TCDD. One potential use for this assay would be the determination of toxic equivalency factors (TEFs) of complex mixtures of dioxin-like compounds. The determination of TEFs of complex and uncharacterized mixtures of dioxin-like compounds is critical for environmental monitonng and cleanup, risk assessment, exposure assessment, and molecular toxicology research. Existing methods to determine TEFs of complex mixtures are not commercially acceptable due to the need for live cells, radioactivity, or sophisticated equipment. We propose the determine toxicological relevance of measuring the in vitro transformation of the Ah receptor. These studies will provide a bioassay acceptable to a wide variety of scientists involved in dioxin toxicology research.
