stress protein synthesis: emf interaction with dna prof. martin blank columbia university new york,...
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Stress protein synthesis: EMF interaction with DNA
Prof. Martin Blank
Columbia University
New York, NY, USA
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)
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
ELF: Epidemiology of leukemia
• Wertheimer & Leeper, 1979
• EMF- RAPID Report to US Congress (1999)
‘EMF…not entirely safe…minimize 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’
RF: Cell Phones and Brain Tumors
Hardell et al, 2008 study of wireless phones10 years latency period, use on same side
Malignant brain tumors (e.g., glioma)
OR = 2.7, 95% CI=1.3-6.0 (mobile)
OR = 2.1, 95% CI=0.97-4.6 (cordless)
Highest risk: age<20 years for first use
OR = 5.2
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• RR>5 at 3km, 1µW/cm2, (power density ~1000
times lower than safety standard)
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)
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
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 25:642-646, 2004)
Conclude: EMF safety standards
- based on biological responses, not SAR
- include combined effects of frequencies
Human DNA is ~2 meters long and has ~3 billion base pairs
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
-230-230 -160-160 +1 (bp)+1 (bp)-320-320 -192-192 -107-107 -68-68-100-100-166-166
HSPHSPMYCMYC AA
HSP70HSP70
Sp1Sp1 AP-2AP-2 HSEHSE Sp1Sp1 AP-2AP-2 HSEHSE SRESRE
AATFTF
TTAATTAA
Sp1Sp1 AP-2AP-2
HSPHSPMYCMYC CC
HSPHSPMYCMYC BB
Temperature DomainTemperature Domain (thermal)(thermal)
EMF EMF DomainDomain(non-(non-thermal)thermal)
. .
EMF Specific Domain in HSP70
Lin et al (1999) J Cellular Biochem 75:170-176.
EMF-Specific DNA can be moved
countscounts
Chloramphenicol transferase Chloramphenicol transferase (CAT) Activity(CAT) Activity
00
1010
2020
3030
4040
5050
6060
BBaacckkggrroouunnddEEMM
NNeeggaattiivvee CCoonnttrrooll
Luciferase ActivityLuciferase Activitycountscounts
00
1010
2020
3030
4040
5050
6060
BBaacckkggrroouunnddEEMM
NNeeggaattiivvee CCoonnttrrooll
Experimental ConditionsExperimental Conditions Experimental ConditionsExperimental Conditions
Lin et al (2001) J Cellular Biochem 81:143-148.
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 322:243, 2008)
• pyrimidines (CT) H-bond with purines (GA)
- smaller, smoother surface on splitting
- greater repulsion
- fewer multiple H-bonds
Biological Thresholds in the ELF Range
Biological System Threshold Reference Biochemical reaction rates
Na,K-ATPase 2-3mG Blank & Soo, 1996cytochrome oxidase 5-6mG Blank & Soo, 1998ornithine decarboxylase ~20mG Mullins et al, 1999Belousov-Zhabotinsky <5mG Blank & Soo, 2001
Biosynthesis of stress proteinsHL60, Sciara, yeast, <8mG Goodman et al,1994breast (HTB124, MCF7) <8mG Lin et al, 1998 chick embryo (anoxia) ~20mG DiCarlo et al, 2000
Disease relatedblock melatonin inhibition of breast carcinoma 2<12mG Liburdy et al, 1993leukemia epidemiology 3-4mG Ahlbom et al, 2000
Greenland et al,2000
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)
DNA Stimulation in Muscle
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/m>>3mV/m (HL60)
10V/m>>0.5mV/m (Na,K-ATPase)
Hartner et al (1989) Eur J Biochem
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
BioInitiative Recommendation
Biologically-based precautionary standards
ELF 1-2mG (vs. ~1G)
RF 0.1µW/cm2 (vs. ~1mW/cm2)
micro vs. milli