Abstract: BACKGROUND AND AIM: To explore the effect of selenium on arsenic-induced cell cycle changes by regulation of activator protein-1 (AP-1). MATERIALS AND METHODS: JB6-CI41 cells were exposed to sodium selenite alone at the concentrations of 2.5 μmol/L or combined with arsenous acid at the concentrations of 3.125, 6.25, and 12.5 μmol/L. The AP-1 DNA binding activity and cell cycle were analyzed by electrophoretic mobility shift assay (EMSA) and flow cytometry. Meanwhile, curcumin (20 μmol/L), a specific inhibitor of AP-1, was used to treat JB6 cells together with arsenous acid(12.5 μmol/L) in order to understand the relationship between arsenic-induced cell cycle changes and AP-1 DNA binding activity. RESULTS: Compared with solvent control, arsenous acid (3.125, 6.25 and 12.5 μmol/L) could significantly up-regulate AP-1 DNA binding activity and reduce G1 phase cells (P<0.01,P<0.01), and higher concentrations of arsenous acid (6.25 and 12.5 μmol/L) increased G2 phase cells (P<0.05,P<0.01). Sodium selenite (2.5 μmol/L) showed no effect on AP-1 DNA binding activity and cell cycle(P>0.05,P>0.05). Compared with corresponding concentrations of arsenous acid, co-exposure of JB6-CI41 cells to sodium selenite (2.5 μmol/L) and arsenous acid (3.125,6.25 and 12.5 μmol/L) down-regulated AP-1 DNA binding activity (P<0.01), increased G1 phase cells (P<0.01), and decreased G2 phase cells (P<0.05). Co-exposure of JB6-CI41 cells to curcumin and arsenous acid could significantly down-regulate AP-1 DNA binding activity, increased G1 phase cells and decreased G2 phase cells compared with corresponding concentrations of arsenous acid(all P<0.01). CONCLUSION: Arsenic may change cell cycle by activating AP-1 signal pathway. Certain concentration of selenium could down-regulate arsenic-induced AP-1 DNA binding activity, which may be one of the mechanisms that selenium could antagonize the carcinogenetic property of arsenic.

Key words: selenium, arsenic, activator protein-1, cell cycle, carcinogenesis