Ionizing and Non-Ionizing Radiation- Induced Adaptive Response: Findings From E arth to S pace SMJ Mortazavi Prof. of Medical Physics Shiraz University.

Slides:



Advertisements
Similar presentations
Radiation Biology. Radiation Safety Training Biological Effects Washington State University Radiation Safety Office.
Advertisements

Role of Vitamin D in Blood Malignancies Dr Imran Hilal.
Module 4 Biological Effects of Ionizing Radiation
Dose-Response Relationship: Health Effects In Residents at the High Background Radiation Areas of Ramsar, Iran SMJ Mortazavi, Ph.D Associate Professor.
The Cell Cycle and Cancer. Cell signaling: chemical communication between cells. Click on above to go to animation second chemical response inside the.
Essentials of Environmental Health PH 203 Dr. Khaled El-Ezaby
Effects of Etoposide on the Apoptosis of HL-60 Cells Stefanos F. Haddad a, Glaucia V. Faheina-Martins b,c, Demetrius A. M. Araújo b,c a Department of Biology,
Environmental Health III. Epidemiology Shu-Chi Chang, Ph.D., P.E., P.A. Assistant Professor 1 and Division Chief 2 1 Department of Environmental Engineering.
REVIEW OF THE LOW DOSE RADIATION RESEARCH PROGRAM (LDRRP) IN THE DEPARTMENT OF ENERGY OFFICE FOR BIOLOGICAL AND ENVIRONMENTAL RESEARCH.
Distinguished Lecture * * * ALL ARE WELCOME * * * ENQUIRES: Dr. Fei Chen ( Tel: , Chung-Kwang Chou received his B.S.E.E.
What Do Toxicologists Do?
Introduction of Cancer Molecular Epidemiology Zuo-Feng Zhang, MD, PhD University of California Los Angeles.
Radon I Rikhvanov Leonid P., professor, DSc in Geology and Mineralogy Nadeina Luiza V., associate professor, PhD in Philology TOMSK
Outline What is cancer? How do people know they have cancer?
Biological Effects of Ionizing Radiation Stochastic Somatic Effects Radiation induction of cancer Lecture IAEA Post Graduate Educational Course Radiation.
Health Effects of Radiation
Bystander Effects.
Genomic Instability Delayed Genetic Effects. What is Genomic Instability? Often, after being damaged by radiation, cells are able to repair DNA damage.
IMPACTS OF CRITERIA AIR POLLUTANTS ON THE RESPIRATORY HEALTH OF CHILDREN John R. Balmes, MD UCSF.
Free radicals and antioxidants in health and disease
Understanding Radiation Luiza Gharibyan Yerevan State Medical University.
Tumor genetics Minna Thullberg
Investigating the genetic instability and expression of four DNA repair related proteins in the peripheral lymphocytes of 36 untreated lung cancer patients.
The Challenging Issue of Low Dose Radiation, Hormesis and Adaptive Response: From E arth to S pace S M J Mortazavi Prof. of Medical Physics Shiraz University.
Reactive Oxygen Species April Luna, Mandy Luna, & Tara Monroe.
Adaptive Response to Low Dose Radiation
Oct. 2, 2006 Assignment #2 Due Today Assignment #3 online – Due Wed. Oct. 11 Lab #4 online Quiz #1, Mon. Oct. 16 or Wed. Oct. 18? Examples, Examples Electromagnetic.
Measures of Association
/0409 Copyright ©2004 Business and Legal Reports, Inc. BLR’s Safety Training Presentations Ionizing Radiation 29 CFR
Insert Program or Hospital Logo Introduction Melanoma is notoriously resistant to chemotherapy. While surgical resection and adjuvant chemotherapy can.
Environmental Carcinogenesis White Coat Wonders Lisa Lam Zara Khan.
Group Number: 2 Britney Porter, Sandra Nguyen, Eduardo Vargas and Samender Singh Randhawa.
Chapter 15 Environmental Health, Pollution and Toxicology.
NUCLEAR VS. CHEMICAL CHEMICAL reactions involve rearranging of atoms: e.g., H 2 +O 2  H 2 O No new atoms are created. Chemistry involves electrons only.
SHIP protein identified as a B-cell tumor suppressor Lymphoma is a cancer of the immune system. White blood cells divide again and again, spreading abnormally.
Dr. Antone Brooks Washington State University Tri-cities Richland, Washington Linear-No-Threshold Hypothesis- Scientific Evidence?
Biomarkers Biomarkers - markers in biological systems with a sufficently long half-life which allow location where in the biological system change occur.
Determining the Effect of Triclosan on the Growth of Cancer Cells Lydia Alf and Winnifred Bryant Ph. D. Department of Biology University of Wisconsin,
MAIN TOXICITY TESTING. TESTING STRATEGIES A number of different types of data are used in order to establish the safety of chemical substances for use.
DNA Damage and Biodosimetry
Aging and Reactive oxygen Species. Aging: What is it?  Aging, has been termed generally as a progressive decline in the ability of a physiological process.
W507 – Introduction to toxicology
Cell Aging. Aging is generally characterized by the declining ability to respond to stress, increasing homeostatic imbalance and increased risk of aging-associated.
Biological Effects of Ionizing Radiation Deterministic effects
Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Chapter 4 Radiation Biology.
Russell D. Owen Wireless Phones Russell D. Owen, Ph.D. Chief, Radiation Biology Branch, Division of Life Sciences CDRH Office of Science and Technology.
GASES AND VAPORS thermalA chemical substance where all the molecules are not connected within any sort of structure and so are free to move completely.
QSAR in CANCER ASSESSMENT PURPOSE and AGENDA Gilman Veith Duluth MN May 19-21, 2010.
CATEGORY: VACCINES & THERAPEUTICS HIV-1 Vaccines Shokouh Makvandi-Nejad, University of Oxford, UK HIV-1 Vaccines © The copyright for this work resides.
Targeting of reactive oxygen species can be a potential therapeutic strategy for cancer treatment Ying-Ray Lee 1, San-Yuan Chen 2, and Hau-Ren Chen 3 1.
The Challenging Issue of High Background Radiation Areas SMJ Mortazavi Prof. of Medical Physics Shiraz University of Medical Sciences
Absorbed dose of radiation and its biological influence
Louisiana State University Radiation Safety Office
Prof. of Medical Physics Shiraz University of Medical Sciences
Prof. of Medical Physics Shiraz University of Medical Sciences
Lecture 34 Chapter 3 Book 2 Please turn in term papers by to Kimberly Newman at I would like to be able to share some.
Looking at the other Side of the Coin Stimulatory/Beneficial Effects of Exposure to Mobile Phone Radiation SAR Mortazavi & SMJ Mortazavi Medical Student.
پدید آورنده:علی عموکاظمی
Effects of space radiation on inflammatory infiltration and cell death in the heart and retina Vijayalakshmi Sridharan1, Xiao-Wen Mao2, Maohua Cao1, Preeti.
Electromagnetic Radiation
Bystander Effects.
Cancer Genetics Genetics.
Adaptive Response to Low Dose Radiation
Genomic Instability Delayed Genetic Effects.
Health Effects of Radiation
Using Mode of Action to Reduce Uncertainty in Risk Estimates
Stem cell Basics.
Cell phone radiation risks
Biological Effects of Ionising Radiation
Presentation transcript:

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 1

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

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: Mortazavi SMJ, Ph.D 3

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 4

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 5

6

7

8

9

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 mSv per 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. Akiba Eds, pp , Elsevier, Amsterdam,

Mortazavi SMJ, Ph.D Study Design Ramsar was 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. Akiba Eds, pp , Elsevier, Amsterdam,

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. Akiba Eds, pp , Elsevier, Amsterdam,

Mortazavi SMJ, Ph.D Surprising Results Our study showed that the highest lung cancer mortality rate was in Galesh Mahaleeh, 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. Akiba Eds, pp , Elsevier, Amsterdam,

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. Akiba Eds, pp , Elsevier, Amsterdam,

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. Akiba Eds, pp , Elsevier, Amsterdam,

Mortazavi SMJ, Ph.D 16 The Study of Tumor Markers in 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.

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. Mortazavi SMJ, Ph.D 17

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. Mortazavi SMJ, Ph.D 18

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. Mortazavi SMJ, Ph.D 19

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

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 21

Mortazavi SMJ, Ph.D 22

Adaptive Response Mechanisms Small doses of radiation appear to:  Stimulate protective responses  Triggering DNA repair mechanisms  Elimination of severely damaged cells Mortazavi SMJ, Ph.D 23

Mortazavi SMJ, Ph.D 24

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

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

Genetic Basis? Mortazavi SMJ, Ph.D 27

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

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

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

Mortazavi SMJ, Ph.D 31

Mortazavi SMJ, Ph.D 32

Mortazavi SMJ, Ph.D 33

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

Radiofrequency-Induced Adaptive Response In 2009, it was found for the 1 st 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). Mortazavi SMJ, Ph.D 35

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). Mortazavi SMJ, Ph.D 36

Mortazavi SMJ, Ph.D 37

Mortazavi SMJ, Ph.D 38

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). Mortazavi SMJ, Ph.D 39

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). Mortazavi SMJ, Ph.D 40

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). Mortazavi SMJ, Ph.D 41

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). Mortazavi SMJ, Ph.D 42

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

Window Theory Mortazavi SMJ, Ph.D 44

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 mGy for a single low dose rate exposure” (Mitchel 2010) 45

Mortazavi SMJ, Ph.D 46

Mortazavi SMJ, Ph.D 47

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 Mortazavi SMJ, Ph.D 48 Jin et al. 2012

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. Mortazavi SMJ, Ph.D 49 Jin et al. 2012

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

Mortazavi SMJ, Ph.D 51

Window Theory in Non-Ionizing Radiation-Induced Adaptive Responses Dear Editor, I read with great interest an article by Jin et al. “The Effect of Combined Exposure of 900 MHz Radiofrequency Fields and Doxorubicin in HL-60 Cells", published in the Sep 2012 issue of PLOS ONE Journal (Jin et al. 2012). The authors of the article reported some interesting findings on the induction of adaptive response by pre-exposure of HL-60 Cells to radiofrequency (RF) radiations. As summarized in Table 1, the viability of the cells exposed to DOX alone was 70.2 ± 0.2 while when cells were exposed to 900 MHz RF radiation at 12 μW/cm2 before treatment with DOX, the viability was 82.8 ± 2.1 (P<0.01). RF exposure at higher power densities significantly decreased the viability (60.7 ± 0.5 and 58.6 ± 0.5 for 120 μW/cm2 and 1200 μW/cm2, respectively). On the other hand they reported that they had previously conducted a preliminary experiment to determine the minimum power density for RF pre- exposures to minimize the damage induced by subsequent exposure to DOX. Mortazavi SMJ, Ph.D 52

Non-responsiveness Phenomenon Lack of AR in Some Individuals Reported by: Ikushima, T., and Mortazavi SMJ. Radioadaptive response: its variability in cultured human lymphocytes, In: Biological effects of low dose radiation, Yamada T, Mothersil C, Mich BD and Potten CS (eds), pp 81-86, Mortazavi SMJ, Ikushima T, and Mozdarani H. Variability of chromosomal radioadaptive response in human lymphocytes. Iran. J. Radat. Res., 1(1): , Mortazavi SMJ, Ph.D 53

Immunological Implications of RF-Induced Adaptive Response Mortazavi SMJ, Ph.D 54

Immune System & Space Research  Immune system is highly susceptible to different stressors exist during space flight (Gridley et al., 2009).  Dysregulation of the immune system during and immediately following space missions (Crucian et al., 2011, Crucian et al., 2008).  Despite the well-known reversible immunological alterations in short-term spaceflights, the bioeffects of long-duration spaceflight on neuroimmune responses have not been completely known so far (Stowe et al., 2011).  Solar and galactic radiation are associated with increased risk of infection during long term stay of human outside the Earth’s magnetic field (Zhou et al., 2012). Mortazavi SMJ, Ph.D 55

Implications of RF-Induced Adaptive Response Mortazavi et al. have also recently shown that pre-exposure of BALB/c mice to radiofrequency radiation emitted from a GSM mobile phone increases their resistance to a subsequent bacterial infection (E. coli infection) (Mortazavi et al., 2012b). Mortazavi SMJ, Ph.D 56

Implications of RF-Induced Adaptive Response  Although there is a report by Plews et al. that indicates the induction of adaptive response induced by low-dose whole-body radiation treatments prolonged the survival of prion-infected mice by reducing oxidative stress (Plews et al., 2010), to the best of our knowledge our study was the first study which showed the induction of adaptive response as prolonged survival of Escherichia coli-infected BALB/c mice by pre-exposure to radiofrequency radiation (non-ionizing radiation). Mortazavi SMJ, Ph.D 57

Mortazavi SMJ, Ph.D 58

Mortazavi SMJ, Ph.D 59

Mortazavi SMJ, Ph.D 60

Mortazavi SMJ, Ph.D 61 Source: Mortazavi SMJ, Motamedifar M, Mehdizadeh AR, Namdari G, Taheri M. The Effect of Pre-exposure to Radiofrequency Radiations Emitted from a GSM Mobile Phone on the Suseptibility of BALB/c Mice to Escherichia coli. Journal of Biomedical Physics and Engineering. 2012; 2(4):

Adaptive Response in Space Research Concluding Remark: Exposure of astronauts to continuous isotropic galactic cosmic radiation or low levels of radiofrequency radiation can increase their resistance against solar particle events or infections caused by life-threatening microorganisms. Mortazavi SMJ, Ph.D 62

Implications of RF-Induced Adaptive Response in Space Research Mortazavi SMJ, Ph.D 63

Adaptive Response in Space Research  In a report entitled “Adaptive response studies may help choose astronauts for long-term space travel”, which published in "Advances in Space Research" (Mortazavi et al., 2003), it was previously hypothesized that screening of the candidates of deep space missions by Ground-based in vitro adaptive response tests before any mission can be used to identify the individuals who respond well to low levels of ionizing radiation and reveal high magnitudes of radioadaptive response (Mortazavi et al., 2005). Mortazavi SMJ, Ph.D 64

Mortazavi SMJ, Ph.D citations according to Scopus

Mortazavi SMJ, Ph.D

Two years after Mortazavi et al 2003 report, NASA agrees that adaptive response is a puzzling issue in space radiobiology 2005-Cancer specialist Dr. John Dicello “Cells often react in unexpected ways to radiation, notes Dicello. For example, there's a puzzling phenomenon known as adaptive response. Sometimes, when tissue is exposed to damaging radiation, it not only repairs itself, but also learns to repair itself better next time. How that works is still being investigated” “The damage could be less than the two kinds added together -- or it could be more! There could, perhaps, be an adaptive response in which lightweight solar protons stimulate repair processes to help reduce the effects of the heavy cosmic ray ions. Or something totally unexpected could happen”. Mysterious Cancer Mortazavi SMJ, Ph.D 67

Mortazavi SMJ, Ph.D 68 George et al. 2007: “This study of adaptive response is very interesting and it is important that the phenomenon be investigated further. Four years after Mortazavi et al 2003 report, in 2007:

Durante and Manti 2008: “Another possibility is that an adaptive response to the space environment takes place after the first exposure, which may confer the exposed individual an increased radioresistance. Such a response would be similar to that hypothesized to explain the apparent lack of adverse health effects in VHBRA and HBRA residents. As pointed out by Mortazavi et al. (2003), radiobiological studies on these areas may lead to the identification of the cellular and molecular mechanisms by which susceptibility to genetic damage and cancer is decreased by chronic radiation exposure, hence helping the astronaut selection process.” Mortazavi SMJ, Ph.D 69

Mortazavi SMJ, Ph.D 70

Mortazavi SMJ, Ph.D Mortazavi et al., Advances in Space Research, Vol 31, No. 6, ,

RF-Induced Adaptive Response in Space Research Different methods that can be used for reducing the risk of radiation during deep space missions Mortazavi SMJ, Ph.D 72

Mortazavi SMJ, Ph.D 73

Mortazavi SMJ, Ph.D 74

Mortazavi SMJ, Ph.D 75

References: Bose Girigoswami, K., Ghosh, R. Response to gamma-irradiation in V79 cells conditioned by repeated treatment with low doses of hydrogen peroxide. Radiat Environ Biophys 44, 131-7, Cao, Y., Xu, Q., Jin, Z.D., Zhou, Z., Nie, J.H., Tong, J. Induction of adaptive response: pre- exposure of mice to 900 MHz radiofrequency fields reduces hematopoietic damage caused by subsequent exposure to ionising radiation. Int J Radiat Biol 87, 720-8, Cejas, P., Casado, E., Belda-Iniesta, C., et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control 15, , Crucian, B., Stowe, R., Quiriarte, H., Pierson, D., Sams, C. Monocyte phenotype and cytokine production profiles are dysregulated by short-duration spaceflight. Aviat Space Environ Med 82, , Crucian, B.E., Stowe, R.P., Pierson, D.L., Sams, C.F. Immune system dysregulation following short- vs long-duration spaceflight. Aviat Space Environ Med 79, , Day, T.K., Zeng, G., Hooker, A.M., Bhat, M., Turner, D.R., Sykes, P.J. Extremely low doses of X-radiation can induce adaptive responses in mouse prostate. Dose Response 5, , Dimova, E.G., Bryant, P.E., Chankova, S.G. Adaptive response: some underlying mechanisms and open questions. Genet. Mol. Biol. 31, , Esmekaya, M.A., Ozer, C., Seyhan, N. 900 MHz pulse-modulated radiofrequency radiation induces oxidative stress on heart, lung, testis and liver tissues. Gen Physiol Biophys 30, 84-9, Feinendegen, L.E., Bond, V.P., Sondhaus, C.A., Altman, K.I. Cellular signal adaptation with damage control at low doses versus the predominance of DNA damage at high doses. C R Acad Sci III 322, , Mortazavi SMJ, Ph.D 76

Feinendegen, L.E., Bond, V.P., Sondhaus, C.A., Muehlensiepen, H. Radiation effects induced by low doses in complex tissue and their relation to cellular adaptive responses. Mutat Res 358, , Goldberg, Z., Lehnert, B.E. Radiation-induced effects in unirradiated cells: a review and implications in cancer. Int J Oncol 21, , Gridley, D.S., Slater, J.M., Luo-Owen, X., et al. Spaceflight effects on T lymphocyte distribution, function and gene expression. J Appl Physiol 106, , Hattori, S. Current status and perspectives of research on radiation hormesis in Japan. Chin Med J (Engl) 107, 420-4, Jiang, B., Nie, J., Zhou, Z., Zhang, J., Tong, J., Cao, Y. Adaptive response in mice exposed to 900 MHz radiofrequency fields: primary DNA damage. PLoS One 7, e32040, Jiang, B., Zong, C., Zhao, H., Ji, Y., Tong, J., Cao, Y. Induction of adaptive response in mice exposed to 900MHz radiofrequency fields: Application of micronucleus assay. Mutat Res 751, 127-9, Jin, Z., Zong, C., Jiang, B., Zhou, Z., Tong, J., Cao, Y. The effect of combined exposure of 900 MHz radiofrequency fields and doxorubicin in HL-60 cells. PLoS One 7, e46102, Liu, S.Z., Jin, S.Z., Liu, X.D. Radiation-induced bystander effect in immune response. Biomed Environ Sci 17, 40-6, Liu, S.Z., Liu, W.H., Sun, J.B. Radiation hormesis: its expression in the immune system. Health Phys 52, , Makinodan, T., James, S.J. T cell potentiation by low dose ionizing radiation: possible mechanisms. Health Phys 59, 29-34, Mortazavi SMJ, Ph.D 77

Marnett, L.J., Riggins, J.N., West, J.D. Endogenous generation of reactive oxidants and electrophiles and their reactions with DNA and protein. J Clin Invest 111, , Maynard, S., Schurman, S.H., Harboe, C., de Souza-Pinto, N.C., Bohr, V.A. Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 30, 2-10, Mitchel, R.E. The dose window for radiation-induced protective adaptive responses. Dose Response 8, , Mortazavi, S., Cameron, J., Niroomand-Rad, A. The life saving role of radioadaptive responses in long-term interplanetary space journeys. Elsevier, pp , Mortazavi, S., Mosleh-Shirazi, M., Tavassoli, A., et al. A comparative study on the increased radioresistance to lethal doses of gamma rays after exposure to microwave radiation and oral intake of flaxseed oil. Iranian Journal of Radiation Research 9, 9-14, 2011a. Mortazavi, S.M., Cameron, J.R., Niroomand-rad, A. Adaptive response studies may help choose astronauts for long-term space travel. Adv Space Res 31, , Mortazavi, S.M.J. Window Theory in Non-Ionizing Radiation-Induced Adaptive Responses.,.. Dose Response in press, Mortazavi, S.M.J., Mosleh-Shirazi, M.A., Tavassoli, A.R., et al. A comparative study on the increased radioresistance to lethal doses of gamma rays after exposure to microwave radiation and oral intake of flaxseed oil. Iranian Journal of Radiation Research 9, 9-14, 2011b. Mortazavi, S.M.J., Mosleh-Shirazi, M.A., Tavassoli, A.R., et al. Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator. Dose Response in press, 2012a. Mortazavi SMJ, Ph.D 78

Mortazavi, S.M.J., Motamedifar, M., Namdari, G., Taheri, M. Pre-exposure to Radiofrequency Radiations Emitted from a GSM Mobile Phone Increases Resistance to a Bacterial Infection in BALB/c Mice. Journal of Biomedical Physics and Engineering in press, 2012b. Mortazavi, S.M.J., Motamedifar, M., Namdari, G., Taheri, M., Mortazavi, A.R. Counterbalancing immunosuppression-induced infections during long-term stay of humans in space. Journal of Medical Hypotheses and Ideas 7, 8–10, Mortazavi SMJ. Space radiobiology and the new era of induced radioresistance: Should traditional concepts be moved to science history museums? Technology and Health Care in press. Murray, D., Allalunis-Turner, M., Weinfeld, M. VIIIth International Workshop on Radiation Damage to DNA. Int J Radiat Biol 81, , Olivieri, G., Bodycote, J., Wolff, S. Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 223, 594-7, Ozgur, E., Guler, G., Seyhan, N. Mobile phone radiation-induced free radical damage in the liver is inhibited by the antioxidants N-acetyl cysteine and epigallocatechin-gallate. Int J Radiat Biol 86, , Plews, M., Simon, S.L., Boreham, D.R., et al. A radiation-induced adaptive response prolongs the survival of prion-infected mice. Free Radic Biol Med 49, , Samson, L., Cairns, J. A new pathway for DNA repair in Escherichia coli Sannino, A., Sarti, M., Reddy, S.B., Prihoda, T.J., Scarfì, M.R. Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation. Radiation research 171, , 2009a. Sannino, A., Sarti, M., Reddy, S.B., Prihoda, T.J., Vijayalaxmi, Scarfi, M.R. Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation. Radiat Res 171, , 2009b. Mortazavi SMJ, Ph.D 79

Sannino, A., Zeni, O., Sarti, M., et al. Induction of adaptive response in human blood lymphocytes exposed to 900 MHz radiofrequency fields: Influence of cell cycle. Int J Radiat Biol, Scott, B.R., Walker, D.M., Tesfaigzi, Y., Schollnberger, H., Walker, V. Mechanistic basis for nonlinear dose-response relationships for low-dose radiation-induced stochastic effects. Nonlinearity Biol Toxicol Med 1, , Stowe, R.P., Sams, C.F., Pierson, D.L. Adrenocortical and immune responses following short- and long-duration spaceflight. Aviat Space Environ Med 82, , Tapio, S., Jacob, V. Radioadaptive response revisited. Radiat Environ Biophys 46, 1-12, UNSCEAR. SOURCES AND EFFECTS OF IONIZING RADIATION, UNSCEAR 1994 Report to the General Assembly, with Scientific Annexes. United Nations Scientific Committee on the Effects of Atomic Radiation, 1994 Yan, G., Hua, Z., Du, G., Chen, J. Adaptive response of Bacillus sp. F26 to hydrogen peroxide and menadione. Curr Microbiol 52, , Zdrojewicz, Z., Strzelczyk, J.J. Radon treatment controversy. Dose Response 4, , Zeni, O., Sannino, A., Romeo, S., et al. Induction of an adaptive response in human blood lymphocytes exposed to radiofrequency fields: Influence of the universal mobile telecommunication system (UMTS) signal and the specific absorption rate. Mutat Res, Zhou, Y., Ni, H., Li, M., et al. Effect of solar particle event radiation and hindlimb suspension on gastrointestinal tract bacterial translocation and immune activation. PLoS One 7, e44329, Mortazavi SMJ, Ph.D 80

Thank you Mortazavi SMJ, Ph.D 81