Study on the cellular effects of 60 Hz extremely low-frequency and 1.7 GHz Radiofrequency electromagnetic fields

고재성 Graduate School, Yonsei University 2024 국내석사

Electromagnetic field (EMF) is a physical force produced by electrically charged objects, which can originate from natural sources and artificial technologies. EMFs are categorized into various bands based on their frequency. The 60 Hz frequency, classified within extremely low-frequency electromagnetic fields (ELF-EMFs), is used in electric power supply frequencies in many countries. The 1.7 GHz frequency, which is categorized within radiofrequency electromagnetic fields (RF-EMFs), is essential in telecommunications, especially in mobile network technologies. These EMFs become unavoidable parts of our daily environment, making human exposure to them a common occurrence. Considering their ubiquitous presence, this study aimed to understand their potential biological effects on the cellular level. In subject Ⅰ, I showed exposure to 60 Hz ELF-EMF could promote cellular proliferation in HeLa, Huh7, and B103 cell lines. In the 60 Hz ELF-EMF exposed group, increased viability, slightly accelerated cell cycle progression, and elevated Ki-67 expression levels were observed compared to the unexposed group. This effect was mediated by activation of ERK and appeared to occur through mechanisms independent of MEK, implicating alternative pathways or mechanisms in the ELF-EMF-mediated cellular responses. To further elucidate the mechanisms underlying ELF-EMF-induced cell proliferation, RNA sequencing was conducted. Although no significant changes were observed, the RNA-seq of ELF-EMF-exposed cells suggested the possibility of involvement of the calcium signaling pathway. Thus, I measured intracellular calcium levels in ELF-EMF-exposed cells to find no significant change in calcium levels. Additionally, BAPTA-AM, a calcium chelator, was used to assess the role of calcium signaling in ELF-EMF-exposed cells. However, BAPTA-AM did not affect cellular proliferation, and I observed that the mitochondrial ROS induced by BAPTA-AM was partially recovered by exposure to ELF-EMF. These findings suggest that the accelerated cell proliferation by ELF-EMF exposure may also be mediated through ameliorating the mitochondrial ROS. In subject Ⅱ, I examined the effect of continuous exposure to up to 8 SAR of 1.7 GHz LTE RF-EMF on adipose tissue-derived stem cells and Huh7, HeLa, and B103 cells. The proliferation of all cell types, which displayed different growth rates, did not change significantly compared with that of the unexposed controls. Moreover, alteration in apoptotic populations or cell cycle distribution was not observed. When the thermal control system was turned off and the temperature increase induced by the RF-EMF was not controlled during continuous exposure to 8 SAR of LTE RF-EMF, cellular proliferation increased by 35.2% at the maximum. These results suggest that in the absence of thermal effects, 1.7 GHz RF-EMF is unlikely to have significant physiological effects on biological organisms. 전자기장 (EMF)은 자연적인 원천과 인공적 기술로부터 발생될 수 있는 전기로 대전된 물체로부터 발생하는 물리적 힘이다. 이러한 전자기장은 주파수에 따라 다양한 대역으로 분류된다. 극저주파 전자기장 (ELF-EMF)로 분류되는 60 Hz 주파수는 많은 국가의 전력 공급 주파수에 사용되고, 1.7 GHz 주파수는 라디오파 전자기장 (RF-EMF)로 분류되어 특히 이동 통신 기술에서 필수적이다. 이러한 주파수의 전자기장은 일상 환경의 불가피한 부분이며, 따라서 인간에게 노출은 흔하게 일어난다. 이러한 보편성을 고려하여 본 연구에서는 세포 수준에서 그들의 잠재적 생물학적 효과를 확인하는 것을 목표로 하였다. 제1주제에서, 60 Hz ELF-EMF에 노출된 HeLa, Huh7, B103 세포주에서 세포 증식이 촉진될 수 있음을 확인하였다. 이 효과는 ERK의 활성화에 의해 매개되었으며, MEK와 독립적인 메커니즘을 통해 일어나는 것으로 보인다. ELF-EMF에 의해 유도된 세포 증식의 메커니즘을 보다 명확히 확인하기 위해, 세포 내 칼슘 수준 측정을 시도했지만, 결과는 칼슘수준의 유의미한 변화가 없음을 보여주었고, 이 측정은 기술적 한계로 인해 실시간으로 수행되는 않았다. 그러나, BAPTA-AM에 의해 유도된 미토콘드리아 활성산소종 (ROS)가 ELF-EMF에 의해 부분적으로 감소하는 것을 관찰하였다. 이러한 결과는 ELF-EMF 노출에 의한 세포 증식 효과가 미토콘드리아를 통해 매개될 수도 있음을 시사한다. 제2주제에서는 1.7 GHz RF-EMF에 지속적으로 최대 8SAR의 세기로 노출된 HeLa, Huh7, B103 세포주 및 ASC 세포의 생리학적 영향을 조사하였다. 서로 다른 성장률을 보이는 모든 세포 유형의 증식은 노출되지 않은 대조군과 비교하여 유의미한 변화가 관찰되지 않았다. 또한 세포사멸 비율이나 세포 주기 분포의 변화도 관찰되지 않았다. 그러나 열 제어 시스템 없이 RF-EMF에 의해 유발된 온도상승을 통제하지 않을 경우, RF-EMF에 지속적으로 노출되었을 때, 세포 증식은 최대 35.2% 증가하였다. 이러한 결과는 열 효과가 없는 경우, 1.7 GHz RF-EMF가 유기체에 유의미한 생리학적 영향을 미치지 않을 가능성이 크다는 것을 시사한다.

Continuous exposure to 60 Hz extremely low frequency electromagnetic field promotes human cell proliferation

서동화 Graduate School, Yonsei University 2021 국내석사

전선은 도시 전역에 분포되어 현대문명을 유지하도록 하고, 대부분의 전선은 극저주파 전자기장 (ELF-EMF, extremly low-frequency electromagnetic fields)을 생성한다. 그러나 극저주파 전자기장이 인체에 미치는 생리적 영향에 대해서는 여전히 논란이 많다. 이 연구는 60 Hz의 극저주파 전자기장 중, 강한 에너지 준위인 10-20 mT 사이의 EMF가 세포에 미치는 효과에 대해 탐구하는 것을 목표로 한다. 본 연구에서는 자궁 경부암 세포 HeLa, 신경모세포종 SH-SY5Y, 간암 줄기 세포 Huh7 및 Hep3B, immortalize된 정상 간세포 MIHA, 그리고 정상 섬유아세포 IMR-90가 사용되었으며, 해당 인체 유래 세포에서 ELF-EMF에 대한 세포 효과를 관찰하였다. 72 시간 동안 지속적으로 ELF-EMF를 노출했을 때, 관찰된 모든 세포에서 세포 증식이 촉진되었다. EMF를 제거하면 증식 촉진 효과가 줄어들고 비노출군에 수렴하여 가역적인 효과로 관찰되지만, 일정 시간동안 지속적인 잔류 효과를 보였다. 또한, 14 mT 세기의 ELF-EMF에 노출된 인체 유래 세포에서 인산화된 Erk1/2의 발현이 증가하여 세포 증식 촉진 효과를 뒷받침했다. 그러나, 유의한 세포주기 변화는 관찰되지 않았다. 뿐만 아니라, CCCP에 의해 정상적인 산화적 인산화가 중단된 경우에도 ELF-EMF의 세포 효과가 지속되었다. 이는 미토콘드리아의 산화적 인산화를 활성화하는 것이 ELF-EMF에 의한 생리적 효과의 주요 기전이 아님을 시사한다. 즉, 본 연구는 10-20mT의 균일한 60Hz 파장을 띠는 극저주파 전자기장이 Erk1/2를 활성화하여 인체 유래 세포의 증식이 증가되는 것을 밝혔으며, 미토콘드리아의 산화적 인산화 활성화 이외의 기전에 대한 가능성을 제시한다. Electrical wire is distributed throughout the city to maintain modern civilization, and the majority of them generate extremely low-frequency electromagnetic fields (ELF-EMF). However, the physiological effect of such EMF on the human body is very controversial. This study aims to observe the cellular effect of strong EMF of 60 Hz, 10-20 mT. Here, we tested the cellular effect of the ELF-EMF on various human cells, including human cervical carcinoma HeLa, neuroblastoma SH-SY5Y, liver cancer stem cells Huh7 and Hep3B, immortalized normal hepatic cell MIHA, and normal fibroblast IMR-90. Cell proliferation was promoted in all cells through continuous ELF-EMF exposure for 72 hours, and its effect was reversible but showed a persistent residual effect for a while after removing the EMF. In human cells exposed to 14 mT ELF-EMF, the expression of phosphorylated Erk1/2 was increased, but significant cell cycle disturbance was not observed. The cellular effects of the ELF-EMF persisted even the oxidative phosphorylation was interrupted by CCCP, suggesting that stimulating mitochondrial oxidative phosphorylation is not the main mechanism of physiological effects triggered by EMF. Taken together, this study strongly suggests that uniform 60 Hz ELF-EMF of 10 to 20 mT increase human cell proliferation by activating Erk1/2.

Enhanced cytotoxic and genotoxic effect of gadolinium under the ELF-EMF irradiation in human lymphocytes

조승현 서울대학교 보건대학원 2012 국내석사

Gadolinium (Gd) is widely used for various industrial and medical purposes, particularly in magnetic resonance imaging (MRI) contrast agent. As there has been a large volume of studies about cyto- and geno- toxicity of Gd, it has been utilized as derivatives by chelation with various ligands. Human exposure to Gd and its derivatives is significantly increasing, posing a high risk of accumulation and retention. It is important to investigate the effect of extremely low-frequency electromagnetic fields (ELF-EMF) on the cyto- and geno-toxicity of Gd, since patients are co-exposed to Gd and ELF-EMF generated by MRI scanner. The aim of this study is to investigate the cyto- and geno-toixcity of Gd and the possible enhancing effect of ELF-EMF on the toxicity of Gd in cultured human peripheral blood lymphocytes by performing micronuclei (MN) assay, single cell gel electrophoresis (Comet) assay, trypan blue dye-exclusion assay, apoptosis analysis using flow cytometry and intracellular reactive oxygen species measurement. MN frequencies were 13.0, 14.0, 15.3 and 17.7 per 1000 cells in Gd treatment cells at concentrations of 0, 0.4, 0.8 and 1.2 mM. ELF-EMF exposure (0.8 mT) increased the frequencies of MN induced by Gd treatment alone; 13.3, 17.0, 20.3 and 25.0 per 1000 cells at each Gd concentrations. ELF-EMF exposure also increased cell death, olive tail moment (OTM), apoptosis and ROS level induced by Gd treatment alone. These results suggest that Gd induces DNA damage, apoptotic cell death and ROS generation in human lymphocytes and ELF-EMF can enhance the cyto- and geno-toxicity of Gd.

전력시설 근로자들의 극저주파 전자파 노출 수준에 따른 인체 영향 평가

박경호 고려대학교 보건대학원 2005 국내석사

Background and Objectives : Recently, the use an electric apparatus has brought into concerns about health risks from exposure to electromagnetic fields. EMF are composed of electric fields and magnetic fields. These fields are produced by a wide range of electric devices, including appliances such as washing machines, microwave ovens, around wiring and by lightening, in dwellings and near electric power lines. Heavy exposure to EMF can occur only in the vicinity of high-voltage overhead transmission lines, close to transformers and underground cables, and also close to large electrical machinery. Several studies have suggested that there is a small excess leukemia risk with magnetic field exposure above 2 mG. At first, Wertheimer & Leeper observed that children living in homes classified as exposed to EMF band(eg. 60Hz) were at higher risk of leukemia, lymphoma, and nervous system tumors than unexposed children in 1979. In this thesis I have investigated the hypothesis of an association between occupational exposure to ELF EMF and the risks of leukemia, cancer, thyroid disease, liver disease and other disease. Therefore, the aim of this study is to investigate whether or not ELF-EMF emitted from electric power station and transformer substation affect some hematologic, tumor marker and blood chemistry parameters of electric utility workers. Methods : This case study examined 6946 electric utility workers who underwent periodic health examination in 2003. The subjects in the experimental and control groups were selected according to exposure level and age. The blood test parameters based on periodic health examination were WBC, RBC, hemoglobin and tumor markers, thyroid function test, liver function test and diabetes mellitus and hyperlipidemia test. Results : The hematologic test results and tumor markers and other parameters under investigation were similar in the two groups but some of parameters such as WBC, LDH, alkaline phosphatase, showed significant difference between the two groups from two sample t-test and one-way analysis of variance (P-value <0.05). The exposure group showed incresed LDH level compared to the control group by two sample t-test. In addition, the abnormal LDH level in the exposure group was observed to be clinically significant by chi-square. However, the levels of WBC and alkaline phosphatase observed were not clinically significant by chi-square (P-value>0.05). Conclusions : These results suggested that ELF-electromagnetic field does not affect most blood test parameters except LDH of electric utility workers

지하공동구에서 특고압 전력케이블의 전자기장 분포를 고려한 안전작업거리 추정

성민영 충북대학교 2022 국내박사

전기가 발견되고 발전기가 발명되면서 전기의 상용화가 시작된 이후 전기는 인류역사상 없어서는 안되는 필수 에너지로 자리매김하였다. 전세계가 전산업의 다방면에 걸쳐 전기를 활용되고 있으며, 사용량 또한 지속적으로 증가하고 있다. 한국의 경우 2020년에 연간 509,269,715MWh의 전력을 소비하고 있다. 이는 전력 통계를 작성하기 시작한 19961년 1,189,386MWh의 428배에 달한다. 그러나 전기 사용량이 증가하면서 전기에 의해 발생되는 전자기장(ElectroMagneticFields, EMF)의 대한 유해성에 대한 우려도 높아지고 있다. 전자기장은 전기장과 자기장의 에너지 흐름을 말하여 흐름방향의 90도의 각도로 확산해 나간다. 전자기장은 전압과 전류의 크기에 비례하여 발생하게 된다. 전기 중에 300㎐ 미만의 주파수를 갖는 극저주파(Extremely Low frequency, ELF)의 유해성에 대한 연구는 1970년대부터 오랜기간 연구되어 왔으나 유해하다는 연구 결과와 무해하다는 연구 결과가 대립되는 상황에서 아직 인체유해성에 대한 명확한 결론은 없는 실정이다. 그럼에도 세계보건기구(World Health Organization, WHO)에서는 1996년 ‘국제 EMF(Electromagnetic Fields) Project’를 설립하여 전자기장에 대한 국제 표준 개발을 장려하였으며, 1998년 미국국립환경건강과학연구소(National Institute Of Environment Health Sciences, NIEHS)에서는 전자기장을 인체발암성물질(possibly carcinogenic to human)인 2B로 결론을 내렸다. 이는 전자기장에 대한 의학적 유해성이 밝혀지지 않았지만 관련성은 충분하다는 의견이 반영된 것이다. 본 연구에서는 세계 각국에서는 전자기장의 유해성을 인지하고 안전한 작업을 위한 노출기준을 바탕으로 하여 전자기장 발생 장소의 안전작업거리를 추정하고자 하였다. 이를 위해 적용된 국제기준은 국제방사선보호협회의 산하기관인 ICNIRP(International Commission on Non-Ionizing Radiaion Protection)에서 1998년과 2010년에 발표한 전자기장의 주파수 대역별 권고치이다. 한국은 과학기술정보통신부고시인 ‘전자파인체노출기준’과 산업통상자원부고시인 ‘특고압 전선로 인체보호기준’에 노출기준을 규정하였으며, 이 노출기준과 근로자의 안전보건을 위한 산업안전보건기준을 바탕으로 제도상의 문제점을 파악하였다. 여기서 산업안전 보건기준에서는 전자기장에 의한 오작동 방지에 대해서만 규정되어 있어 근로자의 안전보건 확보를 위한 규정은 없는 실정이었다. 현재 국내는 765kV, 345kV, 154kV, 22.9kV 등 여러 종류의 특고압 송전선로와 전선이 사용하고 있다. 특고압 전력 송전을 위한 전력 케이블은 한국에서만 2020년 기준 218,719km가 설치되어 있으며 이 또한 전력 소비 등가에 따라 매년 증가하고 있다. 한국의 전력선의 주파수는 60㎐를 사용하고 있으며 전력선을 점검하고 관리하는 작업자는 이러한 극저주파에 수시로 노출되고 있었다. 따라서 본 연구에서는 전자기장에 대한 사회적인 문제를 야기한 전력선을 타켓으로 전자기장을 측정하였다. 우리나라 특고압 송전 전력선 중 154kV와 22.9kV의 전력선에 대해 설치 사례별로 전자기장을 측정하였으며, 측정 결과를 한국의 노출기준과 비교하여 노출기준을 초과하는 구간을 확인하고 인체사이즈를 반영한 안전한 작업거리를 추정하였다. 측정대상 전력선은 ○○신도시의 전력을 공급하는 지하공동구 내에 설치된 154kV와 22.9kV 케이블과 ○○시 하수종말처리장의 메인전력선의 22.9kV와 sub전력선의 22.9kV 로 총 4개의 전력케이블에 대하여 전기장과 자기장을 각각 측정하였다. 따라서 모두 8가지 Case의 측정을 실시하였다. 측정 결과를 분석하고 노출기준을 초과하는 구역을 확인하여 한국인 인체사이즈를 반영한 안전한 작업거리를 추정하였다. 본 연구를 통해 전력케이블에서 발생하는 전자기장 발생 분포 특성을 반영하여 케이블 설치시 안전한 작업공간을 확보하고 위험공간을 작업자에게 시각적으로 제공함으로서 작업자가 심리적으로나 물리적으로 안전하게 작업할 수 있도록 관리하는데 기여할 것으로 기대한다. Ever since electricity was commercialized upon its discovery and the development of generators, it has served as an essential source of energy that people cannot live without in human history. It has been utilized in various areas of all industries across the world, and its usage is on a steady rise as well. As for Korea, for instance, its annual electricity consumption stood at 509,269,715 MWh in 2020. This is a whopping 428 times higher than its annual consumption of 1,189,386 MWh in 1961 when the country started to compile electricity statistics. As the usage goes up, however, there are growing concerns over the potential harmful effects of EMF (Electromagnetic Fields) that are generated by electricity as well. An EMF refers to the flow of energy charges with both electric fields and magnetic fields and spreads at an angle of 90 degrees from the direction of their movement. Electric fields are created in proportion to the size of voltage and current. Although the harmful aspects of ELF (Extremely Low Frequency) with a frequency of less than 300㎐ have been studied for a long time since 1970s, there is no concrete conclusion over its harmful health effects as the results of some studies were validating its negative effects while others were not, contradicting against one another. Nonetheless, the WHO (World Health Organization) established the 'International EMF Project' in 1996 to promote the development of international standards on EMF, and the NIEHS (National institute of environment health sciences) concluded that they were classified as 2B, a category of possibly carcinogenic to human. This tells us that even though their harmful effects have yet to be proven medically, there is a correlation sufficiently notable to reach that conclusion. This dissertation was aimed to create a safe working environment at a distance where EMF are generated based on the exposure limit established for safe operations upon the recognition of the harmful aspects of the fields. The international standard employed for this purpose was the ICNIRP (International Commission on Non-Ionizing Radiation Protection) Guidelines on limiting exposure to electromagnetic fields, which were released both in 1998 and in 2010. Korea established the exposure limit through the 'Limit of Human Exposure to Electric Fields,' a notice released by the MSICT (Ministry of Science and ICT), and the 'Regulations to Protect Persons against Extra-high Voltage Power Line', a notice issued by the MOTIE (Ministry of Trade, Industry and Energy), and problems present in the current systems were identified based on this exposure limit and the ISHS (Industrial Safety and Health Standards), created for the safety and health of workers. The standards, however, defined only the prevention of defects and failures caused by EMF, lacking requirements to secure the safety and health of workers. Currently, Korea employs various types of extra-high voltage transmission lines and electric wires, ranging from 765 ㎸, through 345 ㎸ and 154 ㎸ to 22.9 ㎸. The total length of power cables installed for the transmission of high-voltage power runs up to 218,719 ㎞ as of 2020 in Korea, and increases each year due to a rise in power consumption. The frequency of power lines in Korea is 60 ㎐, and operators inspecting and maintaining these lines were exposed to such an extremely low frequency on a frequent basis. Against this backdrop, this thesis targeted the power lines that brought public attention to EMF to measure their fields. Among the extra-high voltage transmission lines, 154㎸ and 22.9㎸ lines were chosen to measure their EMF when each was installed, and the measurements were compared with Korea's exposure limit to see which section exceeded the limit and to establish a safe working environment based on the human body size. The power lines targeted for the measurement of electric and magnetic fields were a total of four cables, which included the 154 ㎸ and 22.9 ㎸ power cables installed in a common duct to supply electricity to ‘○○ New Town’ and the 22.9 ㎸ main power line and 22.9 ㎸ sub power line in the ‘wastewater treatment facility in the city of ○○’. This lead to a total of eight cases of measurement. The results were analyzed and sections exceeding the exposure limit were identified to set up a safe working space, reflecting the body size of the Korean. This thesis is expected to contribute to the management of such working spaces by securing safe working conditions during an installation of cables and providing visual presentation of potentially dangerous sections to ensure that workers operate in a psychologically and physically safe environment, based on the analysis on the characteristics of generation and distribution of electric and magnetic fields created in power cables.