ABSTRACT
CONTENTS 1.1 Introduction ........................................................................................................................... 1 1.2 Proliferation, Activity, and Function of Lymphocytes................................................... 3
1.2.1 Human Studies ......................................................................................................... 3 1.2.2 Peripheral Blood Cells Cultured Ex Vivo ............................................................. 4 1.2.3 Animal Studies.......................................................................................................... 4
1.3 Cell Death............................................................................................................................... 5 1.3.1 Cell Culture and Peripheral Blood Cells Ex Vivo Studies ................................. 5 1.3.2 Studies in Animals ................................................................................................... 6
1.4 Micronucleus Formation...................................................................................................... 6 1.4.1 Cell Culture and Peripheral Blood Cells Ex Vivo Studies ................................. 6 1.4.2 Studies in Animals ................................................................................................... 7
1.5 Chromosome Damage (Sister Chromatid Exchange, Aberrations, etc.)...................... 7 1.5.1 Studies on Human Subjects .................................................................................... 7 1.5.2 Cells in Culture and Peripheral Blood Cells Cultured Ex Vivo........................ 7 1.5.3 Studies in Animals ................................................................................................... 8
1.6 DNA Damage as Single-Strand and Double-Strand Breaks.......................................... 8 1.7 Leukemia and Lymphoma .................................................................................................. 9 1.8 Possible Mechanisms of Action of Radiofrequency Radiation
and Electromagnetic Field................................................................................................. 10 1.8.1 Ca2þ Homeostasis................................................................................................... 10 1.8.2 Nonthermal Heat Shock Effects ........................................................................... 11 1.8.3 Gene and Protein Activation ................................................................................ 12 1.8.4 Induction of Reactive Oxygen Species................................................................ 12
1.9 Conclusions-Possible Explanations of Contradictory Results .................................. 13 References ..................................................................................................................................... 15
Establishing the biological effects of exposure to electromagnetic fields (EMF), particularly extremely low-frequency (ELF, 0 to 3000 Hz) fields and radiofrequency (RF) radiation, remains an elusive goal to this day. Over the last 20 to 30 y, hundreds of scientists
across the world have used different types of EMF and RF sources and exposure regimens on different biological experimental models, and different types of data analyses have been applied to both experimental and epidemiologic data. Despite the breadth of these studies (or perhaps because of it), no universally accepted hypotheses exist in this field of research. In this chapter, we attempt to present selected examples from the plethora of available material that best emphasize positive and negative findings from the literature pertinent to the immune system and discuss possible causes for the disparity of the published data. Before going further into an exploration of the effects of RF and ELF EMF on the immune
system, we emphasize some unique aspects of this view on the biological effects of EMF. First of all, many studies were done on the cells of the immune system because it is relatively simple to obtain these cells in a noninvasive way from humans and whole organisms; second, many chose to study effects of EMF on the immune system because this system is one of the first to interact with the environment and, it is generally believed, themost likely to be affected by stimuli from the environment. Clearly, cells of the immune system are well attuned to a broad variety of perturbations in the environment. Nevertheless, it is also true that immune cells are very difficult to study for prolonged periods since their lifetime in culture is relatively short; and any stimulus that these cells are exposed to is, of necessity, added to an already long list of stimuli to which the immune cells respond. Therefore, the immune system may be a difficult subject of study when one examines the effects of an agent without a direct target such as EMF exposure. A broad range of different exposure conditions has been used for studies on the
immune system, and often it is difficult to compare studies using such different exposure conditions. Some of the RF radiation qualities used in the studies reviewed here include continuous-wave (CW) or pulsed-wave RF radiation at 1.748, 1.9, or 2.45 GHz with power densities up to 5 mW/cm2 and calculated specific absorption rates (SARs) in biological material between 0.1 and 12 W/kg. Some studies involved microwave (MW) with a frequency of 42.2 GHz, peak power density of 31 + 5 mW/cm2, and peak SARs of 622 + 100 W/kg. Another large group of RF studies included variations of different possible mobile phone type RF-plane wave or CW with frequencies around values of 900 and 800MHz, power densities up to 950W/m2, and SARs between 0.008 and 8.8W/kg. Electric and magnetic fields were, most often, tested with low-frequency (50 to 60 Hz)
and magnetic field intensities between 0.2 and 500 mT. Static electric and magnetic fields were tested as well, often with magnetic intensities as high as 10 T. Furthermore, different investigators used continuous and/or intermittent exposures; according to some authors intermittent exposures are more efficient in causing biological effects, [1] while some case report studies concentrated on exposures that included peaked EMF exposures, such as when a surge occurs as a power line is severed. Homogeneous and gradient static MF exposures were compared, e.g., Hirose and others found the gradient MF to be more biologically effective [2]. EMF pre-, co-, or post-exposures were combined with exposures to chemical (mitomycin C [MMC], vinblastine, and others) and/or physical (gamma-and x-ray ionizing radiation, UVB, and UVA radiation) mutagens or substances that are responsive to magnetic fields but are not genotoxic on their own (FeCl2). Experimental exposure lengths used varied between 5 min and 350 d, while case report studies included exposures that were years in duration. In addition to case report studies and testing of blood samples from humans occupa-
tionally exposed to RF or ELF EMF, planned experiments were set up with biological targets that included human or rodent peripheral blood cells (PBC) exposed ex vivo, cultured cells of lymphoblast and monocyte lineages (Jurkat, HL-60, Mono Mac-6, K-562, U-937, and DG-75), or blood cells derived from exposed animals (Sprague-Dawley rats or mice: Swiss, C57BL/6, BALB/c, DDY, pKZ1, E mu-Pim1).
