MUTAGENIC EFFECTS OF CHROMIUM (IV) ON HUMAN ENDOTHELIAL AND LUNG EPITHELIAL CELLS

Effects of a chromium (IV) compound,diperoxoaquoethylenediaminechromium (IV) monohydrate (Cr(IV)-DPO), on human umbilical vein endothelial cells (HUVEC) and human bronchial epithelial cells (BEAS-2B) were investigated through morphological, cell viability, gene expression, and cDNA sequencing assays. The cell morphology showed both HUVEC and BEAS-2B cells suffered significant but different degrees of damage and demonstrated features indicating carcinogenesis when these cell lines were exposed to Cr(IV)-DPO for different time durations. Results from viability and morphological assays indicated that genotoxic damages of Cr(IV)-DPO to HUVEC and BEAS-2B cells were both concentration and time dependent. With longer time exposure up to 72 hr or higher concentration up to 100 µM, these damages were more pronounced. To understand the specific nature of these damages, expressions of apoptotic and DNA repair genes by RT2-PCR arrays, and cDNA sequencing studies were carried out. Expressions of most apoptotic genes of HUVEC were altered; in particular, they were over-expressed due to the chronic Cr(IV)-DPO exposure (5 µM, 48 hr), indicating that Cr(IV) inhibited cellular proliferation in response to the oxidative damage. When BEAS-2B cells were treated with the same concentration of Cr(IV)-DPO, DNA repair genes displayed responses less actively as the exposure time increased. Gene sequencing experiments on Cr(IV)- treated BEAS-2B cells exhibited remarkable mutations with transverse mutations dominated the variants. These gene mutations were random and not confined to guanine bases as reported in the literature.