Cytotoxicity of Chromium-III and – VI Compounds. I in Vitro Studies Using Different Cell Culture Systems

Abstract

The cytotoxic effects of chromium-3 (Cr-3; as chloride, CrCl₃) and -6 compounds (chro-mates as chromium trioxide, CrO_s; 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 dismu-tase (SOD), catalase, reduced glutathione (CSH), dithiothreitol (DTT), dimethyl sulfoxide (DMSO), EDTA, butylated hydroxytoluene (BHT), desferoxamine, a-tocopherol, and Trolox, respectively. Neither SOD, catalase, DMSO, EDI A, nor CSH prevented cell cytotoxicity in V79 or LEC cell cultures. However, DTT, which is intracellular metabolized to glutathione, was able to reduce chromate-induced cell cytotoxicity, as did the radical scavengers BHT, desferoxamine, and Trolox, a water-soluble α-tocopherol derivate. Chromate cytotoxicity was therefore assumed to be mediated via the decrease of the intracellular CSH pool by either an overwhelming oxidation of CSH and/or inhibition of glutathione reductase. However, an additional mechanism of chromate-induced cytotoxicity must be assumed, because antioxidants were not able to inhibit completely toxic injury of the cells.