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Ionizing and Non-Ionizing Radiation-Induced Adaptive Response: Findings From E arth to S pace

Ionizing and Non-Ionizing Radiation-Induced Adaptive Response: Findings From E arth to S pace. SMJ Mortazavi Prof. of Medical Physics Shiraz University of Medical Sciences mmortazavi@sums.ac.ir. Paracelsus (1493-1541). "All substances are poisons; there is none which is not a poison.

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Ionizing and Non-Ionizing Radiation-Induced Adaptive Response: Findings From E arth to S pace

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  1. Ionizing and Non-Ionizing Radiation-Induced Adaptive Response: Findings From Earth to Space SMJ Mortazavi Prof. of Medical Physics Shiraz University of Medical Sciences mmortazavi@sums.ac.ir

  2. Paracelsus (1493-1541) • "All substances are poisons; there is none which is not a poison. • The right dose differentiates a poison…." Mortazavi SMJ, Ph.D

  3. Hormesis • All chemical substances will exhibit a toxic effect given a large enough dose. • If the dose is low enough even a highly toxic substance will cease to cause a harmful effect. • The toxic potency of a chemical is thus ultimately defined by the dose (the amount) of the chemical that will produce a specific response in a specific biological system. • Source: http://learn.caim.yale.edu/chemsafe/references/dose.html Mortazavi SMJ, Ph.D

  4. LNT & Radiation Hormesis • The radiation hormesis model, unlike the LNT model, assumes that adaptive/protective mechanisms can be stimulated by low-dose radiation and that they can prevent both spontaneous and toxicant-related cancers as well as other adverse health effects (Calabrese et al. 2007). Mortazavi SMJ, Ph.D

  5. Natural radiation deficiency symptoms • It has been long known that protozoa and bacteria exposed to artificially lowered levels of natural radiation demonstrate deficiency symptoms expressed as dramatically decreased proliferation. Mortazavi SMJ, Ph.D

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  10. Mortazavi SMJ, Ph.D Radon & Lung Cancer in Ramsar, Iran • Radon levels in some dwellings are up to 3700 Bq/m3 (over 100 pCi/L). • The people and their ancestors exposed to abnormally high radiation levels over many generations. • If a radiation dose of a few hundred mSvper year is detrimental to health causing genetic abnormalities or an increased risk of cancer, it should be evident in these people. Mortazavi SMJ, M. Ghiassi-Nejad and M. Rezaiean. Cancer risk due to exposure to high levels of natural radon in the inhabitants of Ramsar, Iran in: High Levels of Natural Radiation and Radon Areas: Radiation Dose and Health Effects, T. Sugahara, M. Morishima, M. Sohrabi, Y Sasaki, I. Hayata, and S. AkibaEds, pp. 436-437, Elsevier, Amsterdam, 2005.

  11. Mortazavi SMJ, Ph.D Study Design • Ramsarwas divided into eight health districts and a health center provided primary health services in each health district. • Indoor radon concentration levels were previously measured in each dwelling by the Iranian Nuclear Regulatory Authority experts. Mortazavi SMJ, M. Ghiassi-Nejad and M. Rezaiean. Cancer risk due to exposure to high levels of natural radon in the inhabitants of Ramsar, Iran in: High Levels of Natural Radiation and Radon Areas: Radiation Dose and Health Effects, T. Sugahara, M. Morishima, M. Sohrabi, Y Sasaki, I. Hayata, and S. AkibaEds, pp. 436-437, Elsevier, Amsterdam, 2005.

  12. Mortazavi SMJ, Ph.D Cancer Mortality • The overall cancer mortality, lung cancer mortality and neonatal death rate of different districts in the years from 2000 to 2001 were collected. • The radon prone houses were located in a district named Ramak. Mortazavi SMJ, M. Ghiassi-Nejad and M. Rezaiean. Cancer risk due to exposure to high levels of natural radon in the inhabitants of Ramsar, Iran in: High Levels of Natural Radiation and Radon Areas: Radiation Dose and Health Effects, T. Sugahara, M. Morishima, M. Sohrabi, Y Sasaki, I. Hayata, and S. AkibaEds, pp. 436-437, Elsevier, Amsterdam, 2005.

  13. Mortazavi SMJ, Ph.D Surprising Results • Our study showed that the highest lung cancer mortality rate was in GaleshMahaleeh, where the radon levels were normal. • On the other hand, the lowest lung cancer mortality rate was in Ramak, where the highest concentrations of radon in the dwellings were found Mortazavi SMJ, M. Ghiassi-Nejad and M. Rezaiean. Cancer risk due to exposure to high levels of natural radon in the inhabitants of Ramsar, Iran in: High Levels of Natural Radiation and Radon Areas: Radiation Dose and Health Effects, T. Sugahara, M. Morishima, M. Sohrabi, Y Sasaki, I. Hayata, and S. AkibaEds, pp. 436-437, Elsevier, Amsterdam, 2005.

  14. Mortazavi SMJ, Ph.D Crude Lung Cancer Rate Mortazavi SMJ, M. Ghiassi-Nejad and M. Rezaiean. Cancer risk due to exposure to high levels of natural radon in the inhabitants of Ramsar, Iran in: High Levels of Natural Radiation and Radon Areas: Radiation Dose and Health Effects, T. Sugahara, M. Morishima, M. Sohrabi, Y Sasaki, I. Hayata, and S. AkibaEds, pp. 436-437, Elsevier, Amsterdam, 2005.

  15. Mortazavi SMJ, Ph.D Adjusted Lung Cancer Rate Mortazavi SMJ, M. Ghiassi-Nejad and M. Rezaiean. Cancer risk due to exposure to high levels of natural radon in the inhabitants of Ramsar, Iran in: High Levels of Natural Radiation and Radon Areas: Radiation Dose and Health Effects, T. Sugahara, M. Morishima, M. Sohrabi, Y Sasaki, I. Hayata, and S. AkibaEds, pp. 436-437, Elsevier, Amsterdam, 2005.

  16. Mortazavi SMJ, Ph.D The Study of Tumor Markersin High Background Radiation Areas Source: S Taeb, SMJ Mortazavi, A Ghaderi, H Mozdarani, MR Kardan, SAR Mortazavi, A Soleimani, I Nikokar, M Haghani, A Soofi. Alterations of PSA, CA15.3, CA125, Cyfra21-1, CEA, CA19.9, AFP and Tag72 tumor markers in human blood serum due to long term exposure to high levels of natural background radiation in Ramsar, Iran. International Journal of Radiation Research. in press.

  17. Mortazavi SMJ, Ph.D Why Tumor Markers? • Recently, as no excess cancer rate was reported in these areas by epidemiological studies, we studied the tumor markers in the inhabitants of these areas to shed some light on the impact of high levels of background radiation on cancer induction.

  18. Mortazavi SMJ, Ph.D Methods • The level of background gamma radiation as well as indoor radon was determined using RDS-110 and CR dosimeters. • Thirty five individuals from a high background radiation area (HBRA) and 35 individuals from a normal background radiation area (NBRA) were randomly selected to participate in the study. • Commercial ELISA kits (sandwich type ELISA tests) were used to measure the serum levels of PSA, CA15.3, CA125, Cyfra21-1, CEA, CA19.9, AFP and Tag72 tumor markers.

  19. Mortazavi SMJ, Ph.D Results • Among the eight biomarkers investigated, the means of PSA, CA15.3, CA125, CA19.9 and AFP concentrations between the HBRAs and NBRAs were not different. • However, Cyfra21, CEA and Tag72 in HBRA group revealed significant increases compared to those of NBRA group (P<0.05). • Statistically significant correlation between the external gamma dose as well as indoor radon level and the concentration of CEA (P<0.001), Cyfra-21(P<0.001) and TAG 72 (P<0.001 and 0.01 respectively) biomarkers were also observed.

  20. What is Adaptive Response?Is it different from Radiation Hormesis? Mortazavi SMJ, Ph.D

  21. Adaptive Response When large radiation exposure is preceded by a small “tickle” dose, the effect of the large dose is sometimes diminished Mortazavi SMJ, Ph.D

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  23. Mortazavi SMJ, Ph.D Adaptive Response Mechanisms Small doses of radiation appear to: • Stimulateprotective responses • Triggering DNA repair mechanisms • Eliminationof severely damaged cells

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  25. There seems to be a genetic basis for adaptive response, since it is demonstrated only in specificcell lines, tissues, animal lines and individuals. It is demonstrated only for specificbiological changes. Adaptive response is specific Mortazavi SMJ, Ph.D

  26. Mortazavi SMJ, Ph.D Genetic Basis? Mortazavi SMJ, Ikushima T, and Mozdarani H. Variability of chromosomal radioadaptive response in human lymphocytes. Iran. J. Radat. Res., 1(1): 55 - 61, 2003.

  27. Mortazavi SMJ, Ph.D Genetic Basis?

  28. Natural Radiation & Adaptive Response High levels of natural radiation can induce adaptive responses Mortazavi SMJ, Ph.D

  29. Mortazavi SMJ, Ph.D Two survey meters show dose rates of 142 and 143 µSv/h on contact with a bedroom wall

  30. Mortazavi SMJ, Ph.D The 1st report on the induction of adaptive response in the residents of High Background Radiation Areas (HBRAs) 105 citations recorded by Web of Science

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  34. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response

  35. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response • In 2009, it was found for the 1st time that pre-exposure of cultured cells to radiofrequency radiation induced an adaptive response which increased the resistance of these cells to mytomycin C (Sannino et al. , 2009a).

  36. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response • Mortazavi et al. also found that laboratory animals pre-irradiated with radiofrequency radiation were less susceptible to subsequent lethal effects of high doses of ionizing radiation (Mortazavi et al. , 2011a, Mortazavi et al. , 2012a). • These findings later confirmed by our subsequent reports (Mortazavi et al. , 2011b, Mortazavi et al, 2012a) as well as the very limited published reports that investigated the induction of adaptive response after pre-treatment with microwave radiation (Cao et al. , 2011, Jiang et al. , 2012, Sannino et al. , 2009b, Sannino et al. , 2011, Zeni et al. , 2012).

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  39. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response • As indicated before, Sannino et al. had previously reported that pre-exposure of peripheral blood lymphocytes collected from human volunteers to non-ionizing RF radiation (900 MHz, at a peak specific absorption rate of 10 W/kg for 20 h) increases their resistance to a challenge dose of mitomycin C (100 ng/ml at 48 h) (Sannino, Sarti, 2009b). • Later, they confirmed their previous results and showed that the timing of adapting dose exposure of radiofrequency plays an important role in the process of adaptive response induction (Sannino, Zeni, 2011). 2012).

  40. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response • On the other hand, Chinese researchers have recently shown that pre-exposure of mice to non-ionizing 900 MHz RF induced adaptive response and thus reduced the hematopoietic tissue damage from a subsequent challenge dose of ionizing radiation (Cao, Xu, 2011). • Zeni et al. also showed that when lymphocytes were pre-exposed to RF at 0.3W/kg SAR and then treated with mitomycin C, these cells showed a significant reduction in the frequency of micronuclei, compared with the cells treated with MMC alone (Zeni, Sannino, 2012).

  41. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response • Jiang et al. also recently used a relatively similar method as we did previously (using the gamma radiation as the challenge dose) and indicated that mice pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage and were significantly different from those exposed to gamma-radiation alone (Jiang, Nie, 2012). • It has also been reported that pre-exposure of Human promyelocytic leukemia HL-60 cells to 900 MHz radiofrequency radiation for 1 hour/day for 3 days had a protective effect in hematopoietic tissue damage induced by doxorubicin, a chemotherapeutic drug (Jin et al. , 2012).

  42. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response • More recently, Jiang et al. used the micronuclei (MN) assay as the endpoint and showed that exposure of mice to both adapting (900MHz RF radiation) and challenge (3Gy gamma-radiation) doses (AD+CD) resulted in a significant decrease in MN indices compared to those exposed to CD alone (Jiang et al. , 2013).

  43. Mortazavi SMJ, Ph.D Radiofrequency-Induced Adaptive Response

  44. Mortazavi SMJ, Ph.D Window Theory

  45. Mortazavi SMJ, Ph.D RE Mitchel: “the adaptive response in mammalian cells and mammals operates within a certain window that can be defined by upper and lower dose thresholds, typically between about 1 and 100 mGyfor a single low dose rate exposure” (Mitchel 2010)

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  48. Mortazavi SMJ, Ph.D Doxorubicin • Doxorubicin (DOX or adriamycin) is the most commonly used anticancer drug because of its efficacy against various tumors. • Like many other chemotherapeutic drugs, administration of DOX has toxic effects on hematopoietic cells Jin et al. 2012

  49. Mortazavi SMJ, Ph.D Minimum power density • A preliminary experiment was conducted to determine the minimum power density needed for 900 MHz RF pre-exposure to minimize the damage induced by subsequent exposure to DOX. • Cells were pre-exposed to 900 MHz RF at 12, 120 and 1200 mW/cm2 power density for 1 hour/day for 3 days. Jin et al. 2012

  50. Mortazavi SMJ, Ph.D Jin et al. 2012

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