CYTOTOXICITY OF CHROMIUM-III AND CHROMIUM-VI COMPOUNDS .1. IN-VITRO STUDIES USING DIFFERENT CELL-CULTURE SYSTEMS

The cytotoxic effects of chromium-3 (Cr-3; as chloride, CrCl3) and -6 compounds (chromates as chromium trioxide, CrO3; barium and lead chromates, BaCrO4, PbCrO4; and as potassium dichromate, K2Cr2O7) were tested in an in vitro test battery. V79 hamster lung fibroblasts, rat pneumocytes type II (LEC), human adenocarcinoma cell line (A549), and guinea pig alveolar macrophages (AM) were incubated with different concentrations of Cr-3 and chromates, respectively. Cr-3 caused no cytotoxic damage to the cells, whereas chromates caused a dose-dependent cytotoxicity. Both Cr-3 and chromates were demonstrated by atomic absorption within the cell. Supernatants from AM experiments were shown to contain no fibroblast activating stimuli. It could be assumed that chromates have no fibrogenic properties. In addition, fibroblast growth and cell division were inhibited by chromates but not by Cr-3, as demonstrated by reduced uptake and nuclear incorporation of bromium desoxyuridine (BrDU) into fibroblasts. A prevention of cell cytotoxicity was attempted using superoxide dismutase (SOD) catalase, reduced glutathione (GSH), dithiothreitol (DTT) dimethyl sulfoxide (DMSO), EDTA, butylated hydroxytoluene (BHT), desferoxamine, alpha-tocopherol, and Trolox, respectively. Neither SOD, catalase, DMSO, EDTA, nor GSH prevented cell cytotoxicity in V79 or LEC cell cultures. However, DTT, which is intracellularly metabolized to glutathione, was able to reduce chromate-induced cell cytotoxicity, as did the radical scavengers BHT, desferoxamine, and Trolox, a water-soluble alpha-tocopherol derivate. Chromate cytotoxicity was therefore assumed to be mediated via the decrease of the intracellular GSH pool by either an overwhelming oxidation of GSH and/or inhibition of glutathione reductase. However, an additional mechanism or chromate-induced cytotoxicity must be assumed, because antioxidants were not able to inhibit completely toxic injury of the cells.