Lecture 32, April 18,2016
Chapter 1 Book 2
Assignments
• 1.Read chapter 1 of book 2 for Wednesday
• 2. Papers Due Friday
• 3. Read Chapter 3 of book 2 for Monday
Effects of RF and ELF on Cells
of the Immune System
Tatjana Paunesku and Gayle E. Woloschak
Basic Problems in 2006
on Cell Culture and Animal
Experiments
• 1. No underlying theory to organize a large
number of results.
• 2. Thus many experiments with different results
were the result of the fact that they were
different with respect to variables they did
not measure or in many cases they did not
know were important.
• 3. For example, time in cell life cycle, background
magnetic field etc.
Immune System
• 1. Choice of the immune system in part as it
senses the environment to protect us
therefore we expect it to pick up
environmental signals such EMF.
• 2. However , since it responds to many
stimulus it may be hard to separate the effects
of the EMF.
Issues
• 1. Very large range of exposure parameters
Frequency, Power levels, length of pulses,
repetition rate , mechanism.
• 2. Many different biological material are studied
• 3.Do not understand the biology well enough to
trace cause and effect from EMF to the end
results in health effects.
• 4. Short life time of the cells in the immune
system.
Issues
• 5. Different endpoints for the experiments.
• 6. Multiple sources of stress.
• 7. In vitro vs in vivo. More feedback and repair
processes in vivo.
Example Human Study vs Mice
• 1 Six Human Exposed 8h/d for 5y to 50Hz with
B=0.2 to 6.6µT
• 2. Results total lymphocytes, CD4+ and CD3+
cell count decreases and NK-Killer cells
Increase.
• 3. 6 month later , CD4+ and CD3+ and CD19+
cell counts are +28, +22, and =17%,
respectively
• 4. Another study had contradictory results.
In 12 Swiss Mice
• 1. Exposed for 109 days to same conditions
• 2. Results total lymphocytes, leukocytes,
polymorphonuclear neutrophils, and CD4+
cells were significantly lower in exposed
animals NK killer cell counts were lower.
Other results
• 1, Changes in NK cells for workers in the fields
generated by induction heater.
• 2. Welders had CD4+ and CE8+ cells
decreased.
• 3. Peripheral Blood Cells Cultured Ex Vivo
show changes.
CONCLUSION
• You are getting change but you do not know
what is going on.
Animal Studies
• 1. 900MHz in TEM Cell to GSM at SAR 1 and
2W/kg saw no short term changes. Some
at 1 week and none for 2 or 4 weeks.
• 2. Another set of experiments on showed
changes some times and not at other
times.
• 3. Again says something is happening but you
do not know how the system works.
Chromosome Damage (Sister
Chromatid Exchange, Aberrations, etc.)
• 1. Study of 24 employees in Norwegian
transformer factory high voltage lab showed
twice the median number of sister chromatid
breaks (5 vs. 2.5 per 50 cells) compared to
controls.
• 2. Other experiments show no change in damage
for exposure to 835.62 MHz for FDMA, CW at
68W yielding power density of 860 W/m2;
and the mean SAR was 4.4 or 5.0 W/kg. for 48
and 72hr.
DNA Damage as Single-Strand and
Double-Strand Breaks
• 1. No damage for 2h,2450MHz at 21W and
average SAR= 2.13W/kg
• 2. Another group for CW at 1.9GHz at 10W/kg
for 4 h showed no damage.
• 3. Another group at 900MHz 50W SAR to
10W/kg no damage.
• 4. Another group shows slowing of the repair
processes for 100Hz,1mT and UVB for DNA
by 34%
Leukemia and Lymphoma
• 1. Two conflicting Studies on Leukemia and lymphoma.
• A. For example, in 1997 Repacholi and others found
increased odds’ ratio (OR) of 2.4, P ¼ 0.006, 95%
confidence interval (CI) of 1.3–4.5 for the
development of lymphoma in lymphoma-prone E
mu-Pim1 transgenic mice exposed to pulsemodulated RF fields twice for 30 min/d for up to 18
months (plane-wave fields of 900 MHz with a pulse
repetition frequency of 217 Hz, pulse width of 0.6
ms; incident power densities were 2.6 to 13W/m ,
and SAR of 0.008 to 4.2W/kg, averaging 0.13–
1.4W/kg)
2
Leukemia and Lymphoma
• B. Utteridge and others exposed 120 E
mu-Pim1 heterozygous mice and 120 wildtype mice to GSM-modulated 898.4 MHz
radiation for 1 h/d, 5 d/week at SARs of
0.25, 1.0, 2.0, and 4.0 W/kg in ‘‘Ferriswheel’’ exposure systems for up to 104
weeks (26 months) and found no increase.
Possible Mechanisms of Action of
Radiofrequency Radiation
and Electromagnetic Field
• 1. Direct DNA damage not observed.
• 2. Change in Charge Distribution on proteins
and protein configuration postulated.
• 3. Activation of promoters of c-myc and HSP70
genes.
• 4. Changes in ROS, reactive oxygen species
Ca2+ Homeostasis
• 1 Ca++ is a second messenger.
• 2. One study shows no effect of 915MHz
2W/kg on Calcium concentrations and
another shows an Increase in activated
cells.
• 3. ELF exposure show changes at 60Hz and
100µT
Nonthermal Heat Shock Effects
• 1. Heat Shock Proteins would be better
described as stress proteins.
• 2. At 895 and 91 5MHz ,5.4 mW/kg changes
in chromatin conformation
• 3. Belyaev and Alipov Frequency windows for
strong effects at 8 and 58Hz at 21µT
Gene and Protein Activation
• 1. Increased Binding Activity of DNA to NF-kB
transcription factor 8.2GHz, 1000 pulses/s,
average 50 W/m2; SAR was 10.8 + 7.1W/kg
• 2. HL60 cells to a 0.1 mT at 50 Hz increase
binding to C-AMP
• 3. Exposed to 50 MHz, modulated at 16Hz, 0.2
mT plus 60 V/m leads overexpression of
the ets1 mRNA in Jurkat cells
Induction of Reactive Oxygen Species
• 1. Simko and Mattsson show ELF - EMF
exposure increases ROS in macrophages
• 2. Zmyslony et.al shows combined effects of
930 MHz CW and FeCl2 at 1.5 W/kg
increase ROS
• 3. Ding et.al exposed HL-60 cells to 60 Hz, 5
mT and H2O2 (85 or 100 mM)
• Showing it as an apoptosis promoter
Planaria Data
ROS Data On Planaria
Conclusions—Possible Explanations of
Contradictory Results
• 1. Biological systems are time dependent.
• 2. There are parallel paths, feedback paths
and repair mechanisms.
• 3. Basic problem is that the biology is not
understood in terms of how the chemistry
and dynamics proceed from one stage to
the next.
• 4. Experiments thought to be the same are
not.