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Mechanisms

Mechanisms. Good-quality investigations. Good Laboratory Practice Blind protocol (double blind for volunteers) Sham exposure (fittizio) Positive control Uniform exposure Dosimetry per organ Temperature control Several exposure levels High-enough statistical power

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Mechanisms

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  1. Mechanisms Rome Jan 06

  2. Good-quality investigations • Good Laboratory Practice • Blind protocol (double blind for volunteers) • Sham exposure (fittizio) • Positive control • Uniform exposure • Dosimetry per organ • Temperature control • Several exposure levels • High-enough statistical power • Independent replication/confirmation Rome Jan 06

  3. Electromagnetic spectrum mm static ELF RF intermediate MRI Induction 50/60 Hz 900, 1800 MHz Transport of electricity Mobile telephony Rome Jan 06

  4. Current density • In the body, the ELF currents (endogenous or induced) circulate between cell because the membrane has a low conductivity (10-8 S/m) (and high capacity 1 µF/cm2) Rome Jan 06

  5. ELF exposure V2 E B50 Hz V1 V1 V2 Rome Jan 06

  6. Effects of induced currents j >1000 mA/m2: fibrillation, major risk 100–1000 mA/m2: stimulation of excitable tissues, health risks, 10–100 mA/m2: visual and nervous effects, bone healing, 1–10 mA/m2 : minor biological effects ? Rome Jan 06

  7. Serotonin receptor(Massot et al. Brain Research 2001) E S Rome Jan 06

  8. Exposure system in vitro Rome Jan 06

  9. ELF exposure system in vitro Madec et al. Bioelectrochemistry, 2003 Rome Jan 06

  10. Experimental studies: cancer Cancerogenesis = multi-phase process 1 Initiation 2 Promotion 3 Progression Modification of anarchic Hyperplasy DNA division metastases Are ELF magnetic fields tumour promotors? Rome Jan 06

  11. nongenotoxic mechanisms genotoxic mechanisms Ca 2+ ODC, melatonine  Proliferation  Apoptosis  DNA repair Genes Damage to DNA Nucleus Cellular Transformation Cytoplasm Rome Jan 06

  12. Experiments on cancer - No initiating effect 4 bioassays : 8 months to 2 years (> 18 hours/day) B = 2, 5, 20, 50, 200, 1000, 2000, 5000 T - No established promoting effect Chemically-induced or tumour-prone animals • Liver cancer (3 studies,negative) • Leukemia/lymphoma(6 studies, negative) • Skin cancer (6 studies, 4 negative) • Mammary cancer (11 studies, 6 positive) No effect Controversy? Rome Jan 06

  13. Experimental studies: genotoxicity Major research effort (> 50 studies) Mutation, micronuclei, chomosome aberrations, DNA fragmentation, DNA repair, etc.) • ELF 50/60 Hz are not genotoxic Synergy with ionizing radiation to elicit mutation with B = 0.1 to 0.5 mT? Rome Jan 06

  14. Experimental studies: Examples  Melatonine Hormone of rythmes biological rhythms, antiradical action - suppression of nocturnal rise of melatonin • in rodents but not in humans… - Suppression of the antiproliferative effect of melatonineon breast cancer cells at B =1.2 µT? Rome Jan 06

  15. Calcium oscillations Rome Jan 06

  16. Conclusions on ELF • Problems • * Epidemiology: classification • * Experimental: reproductibility • Small amplitude of effects • * Epidemiology: low RR for a rare disease • * Experimental: c-jun x 2 vs. TPA: c-jun x 50 • No coherence bet. epidemiology & experimental • * Epidemiology: childhood leukemia • * Experimental: no animal model Rome Jan 06

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