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) ‘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’

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% 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

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 • RR>5 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 25:642-646, 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

11. 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 -192 -166 -160 -107 -100 -68 +1 (bp) -320 A TF T A T A HSP70 Sp1 AP-2 HSE Sp1 AP-2 HSE SRE Sp1 AP-2 EMF Domain (non-thermal) Temperature Domain (thermal) . Lin et al (1999) J Cellular Biochem 75:170-176.

13. 60 N N e e g g a a t t i i v v e e C C o o n n t t r r o o l l B B a a c c k k g g r r o o u u n n d d 50 E E M M 40 30 20 10 0 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 81:143-148.

14. 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

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 <5mG Blank & Soo, 2001 Biosynthesis of stress proteins HL60, Sciara, yeast, <8mG Goodman et al,1994 breast (HTB124, MCF7) <8mG Lin et al, 1998 chick embryo (anoxia) ~20mG DiCarlo et al, 2000 Disease related block melatonin inhibition of breast carcinoma 2<12mG Liburdy et al, 1993 leukemia epidemiology 3-4mG Ahlbom et al, 2000 Greenland et al,2000

16. 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/m>>3mV/m (HL60) 10V/m>>0.5mV/m (Na,K-ATPase)

19. Hartner et al (1989) Eur J Biochem

20. 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) microvs.milli