Evaluation of alterations in antioxidant/oxidant gene expression and proteins following treatment of transformed and normal colon cells with tellurium compounds

Tellurium (Te) is a metalloid, with no known physiologic role in humans. Increasing use of Te compounds in industry such as optical blue ray discs and photographic materials suggests that environmental exposure will increase in the future as these products make their way into land fills. Occupational exposure to individuals involved in production of these products may also occur. However, little has been reported regarding the gastrointestinal toxicity of Te, despite the fact that ingestion represents a likely exposure route. A previous study in our lab has demonstrated that tellurium tetrachloride (TeCl4) causes oncosis and diphenyl ditelluride (DPDT) causes apoptosis via the intrinsic pathway in transformed and normal colon cells. Antioxidant defense systems serve to counterbalance the effects of oxidants and prevent oxidative damage. The purpose of this study was to evaluate the potential of exposure of human transformed and normal cells to tellurium compounds that resulted in metalloid accumulation within cells and to induce oxidative stress by examining the level of heme oxygenase-1 (HO-1), antioxidant/oxidant gene expression and protein alterations following the treatment of HT-29 and CCD-18Co cell lines. Significant increases in metalloid accumulation were observed with 500 microM and 1000 microM DPDT exposure and in 125 microM-1000 microM TeCl4 exposure in HT-29 cells and 500 microM DPDT or TeCl4 exposure in CCD-l8Co cells. Significant increases in HO-1 were observed at concentrations of 250 microM-1000 microM DPDT and 62.5 microM-1000 microM TeCl4 in HT-29 cells. Significant increases were also seen in 500 microM and 1000 microM DPDT and 62.5 microM-1000 microM TeCl4 in CCD-l8Co cells. qPCR was done to evaluate gene expression alterations. A significant increase in COX-2 level was observed at concentrations of 500 microM and 1000 microM DPDT and 125 microM-1000 microM TeCl4. Significant increase in NQO1 was also observed at concentration of 500 microM and 1000 microM DPDT or TeCl4 in CCD-l8Co cells. In HT-29 cells, an increase in Cygb was noted at concentrations of 500 microM and 1000 microM DPDT or TeCl4. NCF-1 increases were noted at exposures of 1000 microM DPDT or TeCl4. No change was observed in inetallothionein-3 (MT-3) in HT-29 cells and glutathione reductase (GR) in CCD-l8Co cells.