Identification of novel dioxin-responsive genes by representational difference analysis.

Representational difference analysis (RDA) was employed on dioxin-stimulated Hepa-1 mouse hepatoma cells (human breast cancer) MCF-7 cells, mouse liver, and mouse thymocytes in order to identify novel responder genes to dioxin. In addition to several clones representing known dioxin-inducible genes, several clones were isolated that represented genes that were previously not known to be inducible by dioxin, including B94 (also known as tumour necrosis factor alpha-induced protein 2 (Tnfaip2), Seven in absentia homologue 2 (Siah2), the mouse homologue of Bob/Gpr15, and S-adenosyl-homocysteine hydrolase (Sahh, Ahcy). Induction of these genes by dioxin in Hepa-1 cells was rapid. Furthermore, induction occurred in the presence of the protein synthesis inhibitor cycloheximide, indicating that in each case induction is a primary response.