CDNA phage display as a novel tool to screen for cellular targets of chemical compounds

Abstract

cDNA phage display is frequently used in drug development to screen for cellular target of drugs. However, in toxicology, cDNA phage display remains unexplored, although it has large potential in this field. In this study, cDNA phage display is demonstrated as a novel tool to screen for interactions between chemical compounds and cellular targets. The knowledge of these target interactions is valuable to have a more complete understanding of the mechanisms of action of chemical compounds. Bisphenol A (BPA) was selected as a model compound for this study. By selection of the cellular proteins that bind BPA with cDNA phage display, it was possible to identify a known cellular target of BPA, tubulin α and a possible novel cellular target of BPA, transforming acidic coiled-coil containing protein 3. Both these cellular proteins are involved in the mechanism of cell division. The disruption of cell division is a known non-genomic effect of BPA. Non-genomic effects are not mediated by differences in gene expression and therefore important mechanistic information might be missed with the widely used differential gene expression techniques for mode of action research. This cDNA phage display technique can provide important additional information about the interaction of chemical compounds with cellular targets that mediates these non-genomic actions and therefore gives complementary information to toxicogenomic studies to obtain a more complete understanding of the mechanism of action of chemical compounds.