Low-dose Radiation Induces Antitumor Effects and Erythrocyte System Hormesis

Yu, Hong-Sheng,Liu, Zi-Min,Yu, Xiao-Yun,Song, Ai-Qin,Liu, Ning,Wang, Hao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Objective: Low dose radiation may stimulate the growth and development of animals, increase life span, enhance fertility, and downgrade the incidence of tumor occurrence.The aim of this study was to investigate the antitumor effect and hormesis in an erythrocyte system induced by low-dose radiation. Methods: Kunming strain male mice were subcutaneously implanted with S180 sarcoma cells in the right inguen as an experimental in situ animal model. Six hours before implantation, the mice were given 75mGy whole body X-ray radiation. Tumor growth was observed 5 days later, and the tumor volume was calculated every other day. Fifteen days later, all mice were killed to measure the tumor weight, and to observe necrotic areas and tumor-infiltration-lymphoreticular cells (TILs). At the same time, erythrocyte immune function and the level of 2,3-diphosphoglyceric acid (2,3-DPG) were determined. Immunohistochemical staining was used to detect the expression of EPO and VEGFR of tumor tissues. Results: The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without low dose radiation (P < 0.05). The tumor growth slowed down significantly in mice pre-exposed to low dose radiation; the average tumor weight in mice pre-exposed to low dose radiation was lighter too (P < 0.05). The tumor necrosis areas were larger and TILs were more in the radiation group than those of the group without radiation. The erythrocyte immune function, the level of 2,3-DPG in the low dose radiation group were higher than those of the group without radiation (P < 0.05). After irradiation the expression of EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from sham-irradiation group. The expression of VEGFR also decreased, and LDR-24h group was the lowest (P < 0.05). Conclusion: Low dose radiation could markedly increase the anti-tumor ability of the organism and improve the erythrocyte immune function and the ability of carrying $O_2$. Low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.

Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

Yim, Ji-Hye,Yun, Jung Mi,Kim, Ji Young,Lee, In Kyung,Nam, Seon Young,Kim, Cha Soon JAPAN RADIATION RESEACH SOCIETY 2017 JOURNAL OF RADIATION RESEARCH Vol.58 No.3

<P><B>Abstract</B></P><P>Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation.</P>

Conclusions and Suggestions on Low-Dose and Low-Dose Rate Radiation Risk Estimation Methodology

Sakai, Kazuo,Yamada, Yutaka,Yoshida, Kazuo,Yoshinaga, Shinji,Sato, Kaoru,Ogata, Hiromitsu,Iwasaki, Toshiyasu,Kudo, Shin'ichi,Asada, Yasuki,Kawaguchi, Isao,Haeno, Hiroshi,Sasaki, Michiya The Korean Association for Radiation Protection 2021 방사선방어학회지 Vol.46 No.1

Background: For radiological protection and control, the International Commission on Radiological Protection (ICRP) provides the nominal risk coefficients related to radiation exposure, which can be extrapolated using the excess relative risk and excess absolute risk obtained from the Life Span Study of atomic bomb survivors in Hiroshima and Nagasaki with the dose and dose-rate effectiveness factor (DDREF). Materials and Methods: Since it is impossible to directly estimate the radiation risk at doses less than approximately 100 mSv only from epidemiological knowledge and data, support from radiation biology is absolutely imperative, and thus, several national and international bodies have advocated the importance of bridging knowledge between biology and epidemiology. Because of the accident at the Tokyo Electric Power Company (TEPCO)'s Fukushima Daiichi Nuclear Power Station in 2011, the exposure of the public to radiation has become a major concern and it was considered that the estimation of radiation risk should be more realistic to cope with the prevailing radiation exposure situation. Results and Discussion: To discuss the issues from wide aspects related to radiological protection, and to realize bridging knowledge between biology and epidemiology, we have established a research group to develop low-dose and low-dose-rate radiation risk estimation methodology, with the permission of the Japan Health Physics Society. Conclusion: The aim of the research group was to clarify the current situation and issues related to the risk estimation of low-dose and low-dose-rate radiation exposure from the viewpoints of different research fields, such as epidemiology, biology, modeling, and dosimetry, to identify a future strategy and roadmap to elucidate a more realistic estimation of risk against low-dose and low-dose-rate radiation exposure.

Chronic low-dose radiation inhibits the cells death by cytotoxic high-dose radiation increasing the level of AKT and acinus proteins via NF-κB activation

Park, Hyung Sun,Seong, Ki Moon,Kim, Ji Young,Kim, Cha Soon,Yang, Kwang Hee,Jin, Young-Woo,Nam, Seon Young Informa Healthcare 2013 International journal of radiation biology Vol.89 No.5

<P><I>Purpose</I>: This study explored the effects of low-dose and low-dose-rate irradiation in human lung fibroblast CCD-18Lu cells and examined the role of AKT (protein kinase B, PKB) in cellular responses.</P><P><I>Materials and methods</I>: We examined cell survival after chronic low-dose irradiation (0.01 Gy or 0.05 Gy) with challenging high-dose (2 or 10 Gy) irradiation. We examined the effect of AKT activation on cell survival after chronic low-dose radiation using transduced cells with retroviral vector expressing constitutively active AKT (CA-AKT).</P><P><I>Results</I>: Chronic low-dose priming irradiation increased cells viability against the challenging high-dose irradiation. Irradiation at 0.05 Gy increased cellular levels of AKT and acinus long form (L) and short form (S). The chronic low-dose radiation promoted cells proliferation in the exogenously expressed CA-AKT cells. It also increased nuclear factor-kappa B (NF-κB) activity in a biphasic induction pattern. Suppression of NF-κB activation by mutant form of inhibitor of kappa B alpha (IκBαM) antagonized the radiation-induced expression of AKT and acinus L and S.</P><P><I>Conclusions</I>: Chronic low-dose radiation increases the levels of AKT and acinus proteins via NF-κB activation, and the NF-κB/AKT pathway responding to chronic low-dose irradiation plays an important role in the radiation adaptive response.</P>

저선량방사선(율)이 야생형 초파리 계통의 발생과 수명에 미치는 영향

이진우,성기문,김차순,남선영,양광희,진영우 大韓産業醫學會 2008 대한직업환경의학회지 Vol.20 No.3

목적: 저선량방상선에 대한 생물학적 효과 연구들의 결과는 세포사멸, 암 발생 증가 등 부정적 효과에서부터 면역 활성촉진, 수명연장 등의 긍정적 효과 즉 호메시스(hormesis)효과까지 다양하게 나타나고 있어 많은 연구자들 사이에서 논란이 되고 있다. 저선량방사선의 긍정적 효과를 세포 수준이 아닌 개체 수준에서 확인하고자 본 실험을 수행하였다. 방법: 이 연구에서는 저선량방사선(률)에 대한 생물학적 현상을 확인하기 위해, 다양한 야생형 초파리 계통에 감마 방사선(급성(acute):0.2, 0.75, 4 Gy, 만성(chronic): 0.2 Gy)을 조사한 후, 그들의 번데기율, 우화율 그리고 수명을 조사하였다. 결과: 급성, 만성 방사선 0.2 Gy가 조산된 Oregor-R은 대조군에 비하여 생존율이 증가되었고, Canton-S는 급성 0.75 Gy가 조사된 경우에만 대조군에 비하여 생존율이 증가되었다. 급성 방사선 4 Gy가 조사된 W118은 번데기율에서 큰 변화가 없는 반면, 우화율의 급격한 감소를 나타내는 특이적 현상을 보였다. 또한, 방사선 조사를 통한 초파리의 수명 연장 확인 실험에서 급성 혹은 만성 방사선 선량율에 의한 효과 Oregon-R에서만 나타났고 다른 계통에서는 그 차이가 관찰되지 않았다. 결론: 이러한 결과를 통해, 저선량방사선은 초파리 계통 간 차이는 있으나,초파리의 번데기율 및 우화율의 증가를 유도하며,수명의 연장 또한 유발하는 것을 확인할 수 있었다. 계통간의 차이가 발생하는 원인에 대한 규명과 초파리의 저선량방사선에 대한 생물학적 현상의 분자적 기전 규명은 후속 연구를 통하여 이루어져야 할 것이다. Objectives: Although ionizing radiation is recognized as being harmful to humans, debate continues regarding the effects of low doses of ionizing radiation. Some studies have reported that low doses of ionizing radiation have a bio-positive effect, namely hormesis, and many researchers have attempted to find concrete and scientific evidence to prove this. To determine whether the discrepancy in effects of low doses of ionizing radiation arises from genetic differences, a study with a multicellular organism system such as fruit flies is needed. Methods: After irradiation at a low-dose rate of gamma radiation with chronic (0.2 Gy) and acute (0.2, 0.75 and 4 Gy), the pupa rate, eclosion rate and life span were examined with various wild type strains of Drosophila melanogaster such as W1118, Oregon-R, and Canton-S. Results: The life span of Oregon-R exposed to both acute and chronic, low-dose radiation (0.2 Gy) was increased. Although there was some difference in the longevity between the acute and chronic radiation rate, no other differences were found. In Canton-S, only acute dose (0.75 Gy) increased the life span, but it did not in W1118. Conclusions: Although there were some differences between wild type fruit fly strains in longevity, the low doses of ionizing radiation extended the life span of D. melanogaster. Further studies need to be carried out to explain the difference according to dose and dose rate of radiation in the tested strains.

Low-dose-rate gamma radiation aggravates titanium dioxide nanoparticle-induced lung injury in mice

Kang Sohi,Lee Hae-June,Son Yeonghoon,Bae Min Ji,Jo Wol Soon,Park Jun Hong,Jeong Sohee,Moon Changjong,Shin In-Sik,Lee Chang Geun,Kim Joong-Sun 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.2

Background Radiation damage and the cellular response has been studied in various direction, however, the synergic effects of radiation damage with environmental pollution on cells or tissues remained poorly understood. In particular, gene and pathway regulation by low-dose radiation exposure remains unclear. Dust and air pollution in Asian countries contains metal oxide and titanium dioxide nanoparticles (TiO2NPs), which exacerbate respiratory distress. Objective To explore the synergic injury of radiation damage with air pollution, we examined the effects of low-dose-rate radiation with TiO2NPs on pulmonary response in mice. Results Thirty-six mice (C57bl/6) were divided into six groups: sham, 0.1 Gy, 0.3 Gy, TiO2NPs, TiO2NPs + 0.1 Gy, and TiO2NPs + 0.3 Gy group. Mice were irradiated at a low-dose-rate at a dose of 0.1 Gy (0.182 mGy/h) and 0.3 Gy (0.554 mGy/h) for 24 days and exposed to TiO2NPs by intranasal injection at a dose of 0.1 mg daily for 4 days (from day 21 to 24). The combination of low-dose-rate radiation and TiO2NPs caused significantly more pulmonary inflammation via MAPK phosphorylation in mice than did each stimulus alone. Conclusion We conclude that while exposure to each of these two distinct stimuli alone does not cause notable lung damage, they may potentially cause lung damage when combined owing to their synergistic effects. Therefore, we should pay attention to the possible combined effects of low-dose radiation and exposure to TiO2NPs, considering their potential danger in patients with respiratory problems.

CHANGES IN BODY AND ORGAN WEIGHTS, HEMATOLOGICAL PARAMETERS, AND FREQUENCY OF MICRONUCLEI IN THE PERIPHERAL BLOOD ERYTHROCYTES OF ICR MICE EXPOSED TO LOW-DOSE-RATE $\gamma$-RADIATION

Kang, Yu-Mi,Shin, Suk-Chul,Jin, Young-Woo,Kim, Hee-Sun The Korean Association for Radiation Protection 2009 방사선방어학회지 Vol.34 No.3

We exposed ICR mice to low-dose (0.2 Gy) and low-dose-rate (0.7 mGy/h) $\gamma$-radiation ($^{137}Cs$) in the Low-dose-rate Irradiation Facility at the Radiation Health Research Institute to evaluate systemic effects of low-dose radiation. We compared the body and organ weights, number of blood cells (white and red blood cells and platelets), levels of biochemical markers in serum, and frequency of micronuclei in polychromatic erythrocytes between low-dose irradiated and non-irradiated control mice. The ICR mice irradiated with total doses of 0.2 and 2 Gy showed no changes in body and organ weights, number of blood cells (white and red blood cells), or frequency of micronuclei in the polychromatic erythrocytes of peripheral blood. However, the number of platelets (P = 0.002) and the liver weight (P < 0.01) were significantly increased in mice exposed to 0.2 and 2 Gy, respectively. These results suggest that a low-dose-rate of 0.7 mGy/h does not induce systemic damage. This dose promotes hematopoiesis in the bone marrow microenvironment and the proliferation of liver cells. In the future, the molecular biological effects of lower doses and dose rates need to be evaluated.

Radiation Exposure during ERCP after F-18 FDG PET Examination and Health Effect

김병일 대한췌담도학회 2013 대한췌담도학회지 Vol.18 No.1 Suppl

The more nuclear medical examinations are clinically used, the more concern about radiation exposure to medical staff is increasing. In this article, radiation exposure to medical staff during ERCP after F-18 FDG PET examination and health effects will be discussed. Using the easy estimation the radiation exposure to medical staff during ERCP after F-18 FDG PET when contact distances of 50, 60, 70, 100 cm, and the contact time with the patient at 10-minute intervals could be made as a table form. According to this table, if ERCP performed for 20 min at a distance of 70 cm 2 hours after injection of 10 mCi F-18 FDG, radiation exposure was estimated 7.88 μSv. Low dose radiation is set less than 100 mSv because there was no direct epidemiological evidence of cancer increase in the Japanese atomic bomb survivors study in this range. So, interpretation of human health effects at low dose radiation range based on radiation biologic experiments. Based on these experimental results, ICRP supports LNT (Linear No Threshold) hypothesis which means cancer incidence or genetic effects are proportional to radiation dose. However, there are opposite hypothesis to LNT also. Therefore, the results about radiation biologic experiments are incomplete and controversial. We are living in the environment, where 0.7 mSv annual natural radiation dose can vary depending on the region. This natural radiation dose is socially well accepted because we cannot control. In hospital radiation worker, radiation exposure of reasonable level should be able to be accepted because one of the principles of radiation protection is as low as reasonably achievable. If there are conflicts about radiation exposure to medical staff in hospital, there is a need to consider whether these conflicts associate with personal radiation acceptance.

저선량 방사선이 인체에 미치는 영향

도경현 대한의사협회 2011 대한의사협회지 Vol.54 No.12

Low dose radiation has been defined as doses in the range under 100 mSv of low linear energy transfer (low-LET) radiation. There are two sources of ionizing radiation: natural and artificial radiation. Medical radiation exposure is the most common artificial radiation exposure. The frequency and volume of medical radiation exposure has markedly increased because of recent developments in medical technology. Radiation protection is now a concern due to the increasing use of computed tomography (CT) scans and diagnostic X-rays. This article introduced several models and hypotheses regarding the possible carcinogenic risks associated with low-LET radiation. Although opinions vary on the health effects of low level radiation exposure, current studies of medical radiation rely on exposure information collected prospectively, including cohort studies such as atomic bomb survivor studies. Although there are differences in perspective, the majority of studies have supported ‘linear-no-threshold model without threshold’ between low-LET radiation and the incidence of cancer risk. There is a need for further studies on medical radiation exposure including CT and positron emission tomography in order to understand the health effects of low-LET radiation, including the cancer incidence.

CHANGES IN BODY AND ORGAN WEIGHTS, HEMATOLOGICAL PARAMETERS, AND FREQUENCY OF MICRONUCLEI IN THE PERIPHERAL BLOOD ERYTHROCYTES OF ICR MICE EXPOSED TO LOW-DOSE-RATE -RADIATION

강유미,신석철,진영우,김희선 대한방사선방어학회 2009 방사선방어학회지 Vol.34 No.3

We exposed ICR mice to low-dose (0.2 Gy) and low-dose-rate (0.7 mGy/h) -radiation (137Cs) in the Low-dose-rate Irradiation Facility at the Radiation Health Research Institute to evaluate systemic effects of low-dose radiation. We compared the body and organ weights, number of blood cells (white and red blood cells and platelets), levels of biochemical markers in serum, and frequency of micronuclei in polychromatic erythrocytes between low-dose irradiated and nonirradiated control mice. The ICR mice irradiated with total doses of 0.2 and 2 Gy showed no changes in body and organ weights, number of blood cells (white and red blood cells), or frequency of micronuclei in the polychromatic erythrocytes of peripheral blood. However, the number of platelets (P = 0.002) and the liver weight (P < 0.01) were significantly increased in mice exposed to 0.2 and 2 Gy, respectively. These results suggest that a low-dose-rate of 0.7 mGy/h does not induce systemic damage. This dose promotes hematopoiesis in the bone marrow microenvironment and the proliferation of liver cells. In the future, the molecular biological effects of lower doses and dose rates need to be evaluated.