Characterization of the Cellular Response During Apoptosis Induction in Cadmium-Treated Hep G2 Human Hepatoma Cells

Abstract

Cadmium is a toxic transition heavy metal of continuing occupational and environmental concern, with a wide variety of adverse effects on regulation of gene expression and cellular signal transduction pathways. Injury to cells by cadmium leads to a complex series of events that can culminate in the death of the cell. It has been reported that cadmium induces apoptosis in many cell lines. However, the morphological characteristics leading to apoptosis or subsequent regeneration in cells exposed to cadmium have not been clarified. We evaluated whether human hepatoma cells maintained in culture undergo apoptosis when exposed to cadmium. Cytotoxic activity of cadmium on Hep G2 cells determined using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay. A DNA ladder assay was performed by electrophoresis. Cell cycle analysis was quantified by flow cytometry. Nuclear morphology was studied by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. Morphologic alterations in culture hepatocytes treated with CdCl2 were observed by transmission electron microscopy. We have demonstrated that apoptosis is a major mode of elimination of damaged HepG2 cells in cadmium toxicity and it precedes necrosis.

Cadmium-induced apoptosis in oyster hemocytes involves disturbance of cellular energy balance but no mitochondrial permeability transition

“…Mitochondrial depolarization in response to cadmium, with the concomitant release of cyt c and activation of caspase-3-like enzymes, has been demonstrated in all mammalian cell types studied to date, including kidney cells, hepatocytes, neurons and, most relevant, immune cells, suggesting that this is a universal mechanism of cadmium-induced apoptosis in mammals (Habeebu et al, 1998;Kim et al, 2000;Galan et al, 2001;Kondoh et al, 2001Kondoh et al, , 2002Wätjen et al, 2002;Aydin et al, 2003;Shih et al, 2004). By contrast, cadmium-induced apoptosis in oyster hemocytes is activated by a pathway fundamentally different from that of the vertebrates and independent of MPT.…”

“…Enhanced cell death in the hemocyte population has the potential to generate an immunosuppressed organism with reduced capacity to resist pathological insults and opportunistic infections. Currently, nothing is known about the mechanisms of chemically induced apoptosis and necrosis in bivalve hemocytes, although pollutant-induced apoptosis has been studied in vertebrates (Fujimaki et al, 2000;Li et al, 2000Li et al, , 2003Pourahmad and O'Brien, 2000;Robertson and Orrenius, 2000;De La Fuente et al, 2002;Wätjen et al, 2002;Aydin et al, 2003;Shih et al, 2004).…”

Effects of cadmium chloride on some mitochondria-related activity and gene expression of human MDA-MB231 breast tumor cells

“…On the other hand, some Authors have produced evidence on the apoptosis-promoting nature of Cd including its ability to induce DNA fragmentation and chromatin condensation in kidney, blood and liver cells [11][12][13]. Although detailed data on the pathway(s) followed are still missing, Cd-induced apoptosis, at least in human myeloid leukaemia HL-60 cells, seems to involve cytochrome c release from mitochondria, that, in turn, may cleave and process caspases thorough the activation of Apaf-1 [14].…”

Cadmium induced apoptotic changes in chromatin structure and subphases of nuclear growth during the cell cycle in CHO cells

“…5 Cell cycle analysis quantified by flow cytometry and nuclear morphology was studied by fluorescence microscopy after cadmium treatment, coming to the conclusion that apoptosis is a major mode of eliminating damaged cells and that apoptosis precedes necrosis. 6 A common feature in the above mentioned toxic effects of cadmium is the change in chromatin structure. Since cadmium induced chromatin changes leading to apoptosis have not been clarified, we attempted to characterize different chromatin structures in a cell cycle dependent manner in CHO cells after exposing cells to low [1 µM] cadmium concentration.…”