Bioeffects of moderate-intensity static magnetic fields on cell cultures

The interaction of static magnetic fields (SMFs) with living organisms is a rapidly growing field of investigation. However, despite the increasing number of studies on the effects of the interacti on of SMFs with living organisms, many gaps in our knowledge still remain. One reason why it is extremely important to deeply understand the true mode of action of MFs on living organisms, is the need to protect human health in consideration of the probable future introduction of new technologies such as magnetically levitated trains and the therapeutical use of MFs (e.g. magnetic resonance imaging, MRI, coupling of MF exposure with chemotherapy). The lack of knowledge of the morphological modifications brought about by exposure to moderate-intensity SMFs prompted us to investigate the bioeffects of 6 mT SMFs on different cell types, by means of light and electron microscopy, confocal laser scanning microscopy and immuno- or cytochemistry. In the present article we report our own and other data from the literature on the morphological studies of the bioeffects of moderate-intensity SMFs. We focus on morphological modifications related to cell shape, cell surface, cytoskeleton, and plasma membrane expression of molecules and charbohydrate residues. The effects of exposure to moderate-intensity SMF for 24 or 48 h, on apoptosis, on apoptotic related gene products, on macrophagic differentiation and on phagocytosis of apoptotic cells in primary cell cultures (transformed or stabilized cell lines) will be also discussed. Moderate-intensity (6 mT) SMFs induced modifications of cell shape, cell surface and cytoskeleton, progressively achieved during the entire period of exposure. In general, at the end of the exposure period, the cells had a less flat shape due to partial detachment from the culture dishes or a more round–elongated shape (in relation to adhesion growth or in suspension growth respectively) with many irregular lamellar microvilli, while the morphology of the organelles remained unmodified. In parallel with cell shape changes, the microfilaments and microtubules, as well as the quantity and distribution of surface ConA-FITC and Ricinus Comm.-FITC labelling sites, were modified in a time-dependent manner. Apoptosis was influenced in a cell type-dependent manner: for some cells spontaneous apoptosis decreased while, for others, it increased to about 20% after 24 h of continuous exposure. The induction of apoptosis was likely due to the increment of [Ca2C]i during exposure. Cell proliferation was only slightly affected. Indeed, in addition to the cell type, the time of exposure was also an important factor in the intensity of the effects produced. Both apoptotic rate and cell and surface shape were influenced by exposure to SMFs when simultaneously administered with apoptogenic drugs. Apoptotic cells were cleared by an efficient and fast process of phagocytosis mediated by specific epitopes, externalized during the formation of the apoptotic cells, on the dead cells and by specific receptors on the phagocytes (both ‘professional’ and ‘nonprofessional’). The recognition of apoptotic lymphocytes as well as of control cells exposed for at least 24 h to 6 mT SMF by liver sinusoidal cells was influenced by the cell surface modifications which both apoptotic or normal exposed cells underwent during the induction of apoptosis or SMF exposure. The degree of macrophagic differentiation of human pro-monocytic U937 cells induced by phorbol ester was decreased by exposure to 6 mT SMFs, with a consequent fall in cell adhesion and increased polarization of pseudopodia and cytoplasmic protrusions. Differentiation alone, or in combination with exposure to SMFs, affects distribution and quantity of cell surface carbohydrate residues, surface expression of markers of macrophage differentiation, and phagocytic capability. The increasing amount of data reporting on the bioeffects of SMFs is leading researchers to an understanding of how important it is to fully understand the mode of action of MFs on living organisms. Indeed, even if the perturbations of biological systems by SMFs are sublethal at shorter times of exposure, these perturbations could, especially at longer times of exposure, evolve into a progressive accumulation of modifications, whose ultimate effects still need to be clarified

Anticancer drug resistance in drug-induced cell death of U937 cells

Cell death and subsequent posmortem changes are integral pars of the normal development and maturation cycle. Cell death occurs by two alternative, oppisite modes: apoptosis, a programmed form of cell death, and necrosis, an unordered and accidental form

Bioeffects of moderate-intensity static magnetic fields on cell cultures

The interaction of static magnetic fields (SMFs) with living organisms is a rapidly growing field of investigation. However, despite the increasing number of studies on the effects of the interacti on of SMFs with living organisms, many gaps in our knowledge still remain. One reason why it is extremely important to deeply understand the true mode of action of MFs on living organisms, is the need to protect human health in consideration of the probable future introduction of new technologies such as magnetically levitated trains and the therapeutical use of MFs (e.g. magnetic resonance imaging, MRI, coupling of MF exposure with chemotherapy). The lack of knowledge of the morphological modifications brought about by exposure to moderate-intensity SMFs prompted us to investigate the bioeffects of 6 mT SMFs on different cell types, by means of light and electron microscopy, confocal laser scanning microscopy and immuno- or cytochemistry. In the present article we report our own and other data from the literature on the morphological studies of the bioeffects of moderate-intensity SMFs. We focus on morphological modifications related to cell shape, cell surface, cytoskeleton, and plasma membrane expression of molecules and charbohydrate residues. The effects of exposure to moderate-intensity SMF for 24 or 48 h, on apoptosis, on apoptotic related gene products, on macrophagic differentiation and on phagocytosis of apoptotic cells in primary cell cultures (transformed or stabilized cell lines) will be also discussed. Moderate-intensity (6 mT) SMFs induced modifications of cell shape, cell surface and cytoskeleton, progressively achieved during the entire period of exposure. In general, at the end of the exposure period, the cells had a less flat shape due to partial detachment from the culture dishes or a more round–elongated shape (in relation to adhesion growth or in suspension growth respectively) with many irregular lamellar microvilli, while the morphology of the organelles remained unmodified. In parallel with cell shape changes, the microfilaments and microtubules, as well as the quantity and distribution of surface ConA-FITC and Ricinus Comm.-FITC labelling sites, were modified in a time-dependent manner. Apoptosis was influenced in a cell type-dependent manner: for some cells spontaneous apoptosis decreased while, for others, it increased to about 20% after 24 h of continuous exposure. The induction of apoptosis was likely due to the increment of [Ca2C]i during exposure. Cell proliferation was only slightly affected. Indeed, in addition to the cell type, the time of exposure was also an important factor in the intensity of the effects produced. Both apoptotic rate and cell and surface shape were influenced by exposure to SMFs when simultaneously administered with apoptogenic drugs. Apoptotic cells were cleared by an efficient and fast process of phagocytosis mediated by specific epitopes, externalized during the formation of the apoptotic cells, on the dead cells and by specific receptors on the phagocytes (both ‘professional’ and ‘nonprofessional’). The recognition of apoptotic lymphocytes as well as of control cells exposed for at least 24 h to 6 mT SMF by liver sinusoidal cells was influenced by the cell surface modifications which both apoptotic or normal exposed cells underwent during the induction of apoptosis or SMF exposure. The degree of macrophagic differentiation of human pro-monocytic U937 cells induced by phorbol ester was decreased by exposure to 6 mT SMFs, with a consequent fall in cell adhesion and increased polarization of pseudopodia and cytoplasmic protrusions. Differentiation alone, or in combination with exposure to SMFs, affects distribution and quantity of cell surface carbohydrate residues, surface expression of markers of macrophage differentiation, and phagocytic capability. The increasing amount of data reporting on the bioeffects of SMFs is leading researchers to an understanding of how important it is to fully understand the mode of action of MFs on living organisms. Indeed, even if the perturbations of biological systems by SMFs are sublethal at shorter times of exposure, these perturbations could, especially at longer times of exposure, evolve into a progressive accumulation of modifications, whose ultimate effects still need to be clarified

Acrylamide-induced U937 cell morphological modifications: a comparison between single treatment and coadministration with apoptotic inducine drugs

Acrylamide is a chemical intermediate used in the production and synthesis of polyacrylamides, that are widely used in different fields including food stuffs and cosmetics. Acrylamide may be released into the environment from waste during its production and the manufacture of polyacrilamides and other polymers. There is sufficient evidence for the carcinogenicity of acrylamide in experimental animals, while still inadeguate data are available to evaluate that in humans. In particular, no data are yet available to determine its effect when challenged, on purpose or accidentally, with transformed cells, also in association with apoptotic-inducing drugs or stress. With this in view, the effect of acrylamide was investigated, at morphological level, when given to U937 cells as a single compound or together with apoptotic inducine drugs, like puromycin or H2O2, or with physical stress, like hyperthermia. Human monocytic leucemia U937 cells readly undergo apoptosis when exposed to inhibitors of protein synthesis (puromycin), oxidative stress (H2O2), or heat shock at 43 °C for 1 h, but not to acrylamide 50 m/ml. The simultaneous incubation of cells with both puromycin, H2O2, or heat shock, and with acrylamide significantly affects the apoptotic rate achieved with the single compound. However, for all treatments (single or double) almost all cells showed modification of shape: distortion of roundness, loss of microvilli and formation of large bleb-like protrusions