Prof. of Medical Physics Shiraz University of Medical Sciences 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

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

Radiofrequency-Induced Adaptive Response 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).

Radiofrequency-Induced Adaptive Response 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).

Mortazavi SMJ, Ph.D

Mortazavi SMJ, Ph.D

Radiofrequency-Induced Adaptive Response 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).

Radiofrequency-Induced Adaptive Response 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).

Radiofrequency-Induced Adaptive Response 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).

Radiofrequency-Induced Adaptive Response 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).

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

Mortazavi SMJ, Ph.D Window Theory

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)

Mortazavi SMJ, Ph.D

Mortazavi SMJ, Ph.D

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

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

Mortazavi SMJ, Ph.D Jin et al. 2012

Mortazavi SMJ, Ph.D

Window Theory in Non-Ionizing Radiation-Induced Adaptive Responses Mortazavi SMJ, Ph.D 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.

Non-responsiveness Phenomenon Mortazavi SMJ, Ph.D 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, 2000. Mortazavi SMJ, Ikushima T, and Mozdarani H. Variability of chromosomal radioadaptive response in human lymphocytes. Iran. J. Radat. Res., 1(1): 55 - 61, 2003.

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

Immune System & Space Research Mortazavi SMJ, Ph.D 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).

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

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

Mortazavi SMJ, Ph.D

Mortazavi SMJ, Ph.D

Mortazavi SMJ, Ph.D 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):139-46.

Adaptive Response in Space Research Mortazavi SMJ, Ph.D 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.

Thank you Mortazavi SMJ, Ph.D