A New Bioassay of Environmental Chemicals Based on Their Effects on Tumor Cell Invasion

Abstract

The tumorigenic action of environmental chemical substances has been variously examined, although the effect on malignancies after tumor occurrence has not been studied well. In this study, we established a bioassay system based on tumor cell invasion as a possible index of tumor malignancy, and evaluated the effect of various environmental chemicals on tumor cell invasiveness. We previously established a simple invasion assay system using fluorescent cells and a culture insert with fluorescence blocking micropore membrane (FBM). In this study, the effect of various environmental chemicals on the migration of green fluorescent protein (GFP) gene-transfected HT1080 fibrosarcoma cells through a Matrigel-coated filter was examined. The invasive ability of GFP-HT1080 cells was enhanced in the presence of phenol, 2,5-dichlorophenol, 2,4,5-trichlorophenol, and lindane, and was inhibited with bisphenol A, benthiocarb and others among 31 environmental chemicals tested. Enhancement of the migration of GFP-HT1080 cells with phenol and halogenated phenol derivatives depended on the number of linked chloride moieties. The morphological change of HT1080 cells in the presence of phenol and polychlorophenols was determined by confocal laser fluorescence microscopy, and we observed that it was partly correlated with the invasive characteristics. Finally, we assessed the invasion assay with combinations of chemical substances. As a result, none of the combinations increased the invasion ability of HT1080 cells. Although the effect of environmental chemicals on tumor cell invasiveness may not directly relate to the malignancy of tumor cell itself, it is possible that it relates the tumor progression and metastases.