The role of biomembranes in chromium (III)-induced toxicity in vitro.
The role of biomembranes in the chronic toxicity of environmentally occurring chromium acetate hydroxide was investigated by using primary human fibroblasts. Transport of chromium acetate hydroxide across the plasma membrane of the cell, and the effects of chromium (III) ions on the plasma membrane as well as other intracellular membranes, were determined during six weeks of continuous exposure by using atomic absorption spectrometry, observation of cell morphology, membrane integrity assays (for lactate dehydrogenase leakage and lysosomal membrane disruption), and mitochondrial assays (for mitochondrial dehydrogenase activity and mitochondrial transmembrane potential analysis). The type of cell death induced by long-term exposure was determined in terms of phosphatidylserine externalisation, caspase-3 activation, and chromatin fragmentation. Chromium acetate hydroxide, at a concentration of 100 micromol/l, accumulated in exposed cells, inflicting plasma membrane damage and suppressing mitochondrial function. Antioxidant co-enzyme Q, at a concentration of 10 micromol/l, partially prevented plasma membrane damage and mitochondrial dysfunction. Exposure to chromium acetate hydroxide produced apoptosis, necrosis and an intermediate type of cell death in primary human fibroblasts. These results show that the plasma membrane and mitochondrial membrane are important targets for chronic chromium acetate hydroxide toxicity, and that this in vitro system holds promise for studying the toxicity resulting from long-term exposure to metal ions.
Rudolf
Emil
E
Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Czech Republic. rudolf@lfhk.cuni.cz
Cervinka
Miroslav
M
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D017608:Chromium Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects* / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009336:Necrosis; D009942:Organometallic Compounds / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014451:Ubiquinone / Q000494:pharmacology
D017608:Chromium Compounds; D004785:Environmental Pollutants; D009942:Organometallic Compounds; D014451:Ubiquinone; D007770:L-Lactate Dehydrogenase