Induction of morphological changes in BEAS-2B human bronchial epithelial cells following chronic sub-cytotoxic and mildly cytotoxic hexavalent chromium exposures

Abstract

Certain hexavalent chromium (Cr(VI)) compounds are well established occupational respiratory tract carcinogens. However, despite extensive studies, the cellular and molecular mechanisms underlying Cr(VI)-induced lung cancer remain poorly understood. In fact, the models used were often suboptimal and yielded conflicting results that were heavily dependent upon the system and experimental conditions employed. Here, we investigated the effects of chronic subcytotoxic and mildly cytotoxic (0.1-2 microM) Cr(VI) exposures on cultures of human bronchial epithelial cells, the main targets of Cr(VI) carcinogenicity. Our studies with the nontumorigenic BEAS-2B cell line suggest that relatively short exposures (h) to sublethal Cr(VI) doses (0.1-1 microM) may render these cells less sensitive to contact inhibition. We have also observed a reduced sensitivity to Cr(VI)-induced apoptosis shortly after the beginning of exposure to a mildly cytotoxic Cr(VI) dose (2 microM). Further studies are needed to determine whether these two phenotypes are involved in the Cr(VI)-induced carcinogenic process. Additionally, evidence gathered in this study strongly points to a Cr(VI) interference with cell adhesion to the substratum and with cell-cell interactions. Finally, by chronically exposing BEAS-2B cells to mildly cytotoxic Cr(VI) doses (1 and 2 microM), we were able to induce changes in cell morphology and pattern of growth characteristic of an early phase of pre-malignant progression.