Identification of novel genes induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin using differential display method

Abstract

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin; dioxin) and related halogenated aromatic hydrocarbons elicit a diverse spectrum of biochemical and toxic responses in laboratory animals and mammalian cells in culture. But the molecular mechanism of TCDD toxicity is still poorly understood. Here, we found that the genes differentially expressed by TCDD. Treatment of HepG2 cells with TCDD followed by differential display analysis showed a significantly different mRNA expression pattern from the untreated cells. The differentially displayed bands were isolated and used as probes in dot blot and northern blot analysis. Only two among 35 isolated differentially displayed bands were positive in dot blot and northern blot analysis. The DNA sequences of two clones were analyzed and compared to previously reported sequences in Genebank through computer search. This Genebank search analysis revealed that one clone is highly homologous with RanBP2 (Ras-related nuclear protein binding protein2; 93%) and the other is an unknown gene. It has been known that RanBP2 has a critical function in signal pathway through nuclear transport. Thus, it is supposed that the identified gene in this study may be a clue elucidating TCDD toxic mechanism.