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 interaction 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 6mT 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 carbohydrate 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 (6mT) 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 24h of continuous exposure. The induction of apoptosis was likely due to the increment of [Ca(2+)]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 24h to 6mT 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 6mT 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.
