Stress protein synthesis: EMF interaction with DNA

1
Stress protein synthesis EMF interaction with
DNA

• Prof. Martin Blank
• Columbia University
• New York, NY, USA

2
Cancer DNA, EMF

• DNA damage believed to initiate cancer
• Exposure to EMF increases risk of cancer
• EMF interacts with DNA (protein synthesis, strand
  breaks) to cause changes, damage
• Specific DNA sequences interact with EMF
• mutations in DNA repair genes increase risk of
  leukemia OR 4.39 Yang et al, Leukemia
  Lymphoma, 2008)

3
EMF-DNA Interaction

• Very weak EMF causes DNA to initiate protein
  synthesis in the stress response
• Very weak EMF accelerates electron transfer
  suggests EMF-DNA interaction mechanism
• EMF interacts with electrons in DNA
• Conclusion
• EMF safety standards need to be revised down by
  several orders of magnitude

4
ELF Epidemiology of leukemia

• Wertheimer Leeper, 1979
• EMF- RAPID Report to US Congress (1999)
• EMFnot entirely safeminimize exposure
• Threshold for leukemia 3-4mG
• Greenland et al, 2000 Ahlbom et al, 2000
• IARC - International Agency for Research on
  Cancer (2002) EMF possible cause of cancer

5
RF Cell Phones and Brain Tumors

• Hardell et al, 2008 study of wireless phones
• 10 years latency period, use on same side
• Malignant brain tumors (e.g., glioma)
• OR 2.7, 95 CI1.3-6.0 (mobile)
• OR 2.1, 95 CI0.97-4.6 (cordless)
• Highest risk agelt20 years for first use
• OR 5.2

6
Sutro Tower RF Study (Cherry, 2002)
Tower 577m Antennas 400-570m FM 54.7kW TV
616kW UHF 18.3MW

• Risk Ratio for all childhood cancers (1937-1988)
• is elevated, falls off with distance from
  antenna
• RRgt5 at 3km, 1µW/cm2, (power density 1000
• times lower than safety standard)

7
Evidence of DNA Damage

• Repair DNA damage in normal biosynthesis
• Damage remains DNA deletions, repeats
• - in older identical twins
• - in autism parents vs children
• EMF adds to DNA damage
• - stimulate biosynthesis, strand breaks
• - mutations in repair genes increase risk of
  leukemia OR 4.39 (Yang et al, Leukemia
  Lymphoma, 2008)

8
Stress Response Molecular Damage

• Stress proteins are synthesized in reaction to
  potentially harmful environmental stimuli
• stress response ... defense reaction of cells
  to damage that environmental forces inflict on
  macromolecules. (Kültz, Ann Rev Physiol, 2005)
• along with stress genes there are genes that
  sense and repair damage to DNA, proteins

9
Stress Response EMF Safety

• stimulated by both ELF (Goodman, Blank, 1998) and
  RF (dePomerai et al, 2002)
• independent of SAR
• - in ELF, SAR 10-12 W/kg (non-thermal)
• - in RF, SAR 10-1 W/kg (thermal)
• (Blank, Goodman. BEMS 25642-646, 2004)
• Conclude EMF safety standards
• - based on biological responses, not SAR
• - include combined effects of frequencies

10
Human DNA is 2 meters long and has 3 billion
base pairs
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Stress Response DNA

• protein synthesis starts with DNA reaction
• different DNA segments for thermal, EM
• ELF, RF use same non-thermal pathway
• nCTCTn sequences in promoter act as EM response
  elements (EMRE)
• introduce EMRE to get EM response

12

EMF Specific Domain in HSP70
HSP
HSP
HSP
MYC
A
MYC
C
MYC
B
-230
-160
1 (bp)
-192
-107
-68
-100
-166
-320
A
TF
T
A
T
A
HSP70
Sp1
AP-2
HSE
Sp1
AP-2
HSE
SRE
Sp1
AP-2
Temperature Domain (thermal)
EMF Domain (non-thermal)

.
Lin et al (1999) J Cellular Biochem 75170-176.

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EMF-Specific DNA can be moved
Chloramphenicol transferase (CAT) Activity
Luciferase Activity
counts
counts
60
50
40
30
20
10
0
Experimental Conditions
Experimental Conditions
Lin et al (2001) J Cellular Biochem 81143-148.
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CTCT in stress protein DNA

• low electron affinities electrons move easily
• fluorescence decay rate shows more rapid energy
  loss than complementary GAGA
• (Schwalb and Temps, Science 322243, 2008)
• pyrimidines (CT) H-bond with purines (GA)
• - smaller, smoother surface on splitting
• - greater repulsion
• - fewer multiple H-bonds

15
Biological Thresholds in the ELF Range
Biological System Threshold
Reference Biochemical reaction
rates Na,K-ATPase 2-3mG Blank Soo,
1996 cytochrome oxidase 5-6mG Blank Soo,
1998 ornithine decarboxylase 20mG Mullins
et al, 1999 Belousov-Zhabotinsky lt5mG Blank
Soo, 2001 Biosynthesis of stress
proteins HL60, Sciara, yeast, lt8mG Goodman
et al,1994 breast (HTB124, MCF7) lt8mG Lin
et al, 1998 chick embryo (anoxia)
20mG DiCarlo et al, 2000 Disease
related block melatonin inhibition of
breast carcinoma 2lt12mG Liburdy et al,
1993 leukemia epidemiology 3-4mG Ahlbom et
al, 2000 Greenland et al,2000
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Plausible Mechanism

• Weak electric and magnetic fields affect electron
  transfer (DNA, enzymes)
• Displacement of electrons in DNA causes local
  charging
• Charging of molecular assemblies causes
  disaggregation (e.g., hemoglobin)
• EMF stimulated electron transfer in DNA leads to
  disaggregation of DNA strands and initiation of
  protein synthesis
• (Blank, EMBM 27 3-23, 2008)

17
DNA Stimulation in Muscle
18
Electric Field Stimulates DNA in Muscle Nuclei

• Muscle action potential
• resting level to peak 100mV
• rise time 1ms
• propagates at 10m/s (10mm/ms)
• in 1ms 100mV over 10mm
• electric gradient 10V/mgtgt3mV/m (HL60)
• 10V/mgtgt0.5mV/m (Na,K-ATPase)

19
Hartner et al (1989) Eur J Biochem
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Scientific Basis for Precaution

• Bioinitiative report, 2007
• An international group of scientists (including
  3 presidents of the Bioelectromagnetics Society)
  and public health policy professionals provided a
  rationale for biologically-based precautionary
  exposure standards
• Pathophysiology, EMF issue, 2009
• Scientists update report with additional
  scientific evidence and reemphasize the need for
  precautionary exposure standards

21
BioInitiative Recommendation

• Biologically-based precautionary standards
• ELF 1-2mG (vs. 1G)
• RF 0.1µW/cm2 (vs. 1mW/cm2)
• micro vs. milli