Although a variety of modern technologies expose humans to low-frequency magnetic fields, very little is known about the mechanisms through which such exposure could produce biological effects. Research supported by NIH project GM-41635 has demonstrated that tissues in the human brain precipitate a ferromagnetic material, magnetite (Fe3O4), as do several human cancer types. Human magnetite crystals resemble closely those precipitated by magnetotactic bacteria and pelagic fish, sharing features such as unique crystal morphology, the alignment of the [111] crystal axes along the particle length, and in being single magnetic domains. These crystals are unique in living organisms because they are permanently magnetized and interact over 106 times more strongly with external magnetic fields than do any other biogenic materials. Biophysical analyses have shown that the mechanical oscillations of magnetosomes can lead to significant biological effects in powerline-frequency magnetic fields. However, nothing is known at present concerning the cellular location, ultrastructure, biochemistry, genetics, or biological function of the magnetite in human tissues. Biophysical estimates of the potential effects of magnetic field exposure are at best tenuous without at least rudimentary knowledge of the ultrastructure. Understanding the biochemistry of magnetite precipitation could help greatly in the problem of locating the magnetite in situ through the use of sensitive immunological techniques. In the higher vertebrates the magnetite concentration is far too small to permit the isolation of magnetosome proteins, but this is not the case in the magnetotactic bacteria or in chiton teeth (Polyplacophoran mollusks). Using 2-dimensional gel electrophoresis, the investigators have already identified 5 proteins present in the bacterial magnetosome membrane of A. magnetotacticum which are not present in the cell membrane. The investigators request support in this proposal to determine partial amino acid sequences for those proteins, and to use standard PCR techniques to sequence the corresponding genes. The investigators will then probe for evolutionarily conserved proteins and genes in the chitons and higher animals (including humans) known to precipitate magnetite. This should ultimately lead to immunological and histological methods for localizing the magnetite in situ.
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