Long Term Effects of Low Dose Radiation Exposure During Late Gestation on Cardiac Metabolism and Oxidative Stress

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Ashley Nemec-Bakk ◽  
Sarah Niccoli ◽  
Caitlund Davidson ◽  
Douglas Boreham ◽  
Simon Lees ◽  
...  
2019 ◽  
Vol 20 (23) ◽  
pp. 6075 ◽  
Author(s):  
Annemarie Schröder ◽  
Stephan Kriesen ◽  
Guido Hildebrandt ◽  
Katrin Manda

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1–2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 507-507
Author(s):  
Vadim Ivanov ◽  
Tatiana Terehovich ◽  
Eugene Ivanov

Abstract Abstract 507 The question of whether child acute leukemia (ChAL) incidence has changed as a result of Chernobyl is of great scientific and public interest. Our initial report (Nature, 1993) showed no increase in the incidence rates (IR) of ChAL in Belarus in the whole group of children (0–14 y.o.) 5 years (1986 – 1991) after accident. This data were confirmed in several European countries. As concerns infant's AL (0–1 y.o.), Petridou et al. reported 2.6 times increase of AL in Greek infants, exposed in utero to Chernobyl radiation. No significant difference in IR was found among children aged 1 – 4 y.o. or older. All epidemiological data concerning separate analysis of infant (0–1 y.o.) ChL was concentrated on the first decade after Chernobyl and no any systematic data is available after 1996. Since 1979 the occurrence of leukemia has been documented accurately through the Registry of Blood diseases. The patients had to be inhabitants of Belarus and were grouped by age at diagnosis. AL diagnostic accuracy was confirmed by the international experts. Rates were standardized directly to the standard world population. We present the age-cohort-period analyses of IR trends of ChAL from 1979 to 2006 in Belarus. It comprised 1077 ChAL cases (0–4 y.o.). Number of cases and equivalent doses of whole body radiation exposure was tabulated by age at diagnosis and period of observation (seven pre-accident years, 1979–1985) and post-accident 7-year periods: 1986–1992, 1993–1999 and 2000–2006. During first 7 years after the accident (1986–1992) the IR of infant AL (0–1 y.o.) increased significantly – from 49 (IR=4.33) before Chernobyl to 67 cases (IR=6.36) in 1986–1992 (RR=1.47; p=0.04). Older age group (1–4 y.o.) did not show any increase in ChAL rates. Following 7-years period (1993–1999) revealed the statistically significant decrease of incidence of infant leukemia: from 49 (IR=4.33) before Chernobyl to 16 cases (IR=2.29) in 1993–1999 years (RR=0.53; p=0.024). Surprisingly, during the next 7 years (2000–2006) we found a further decrease of the incidence of infant leukemia with only 3 cases (IR=0.47) in 7 years. It is highly significant when compared with 49 cases (IR=4.33) before Chernobyl (p= 0.0000053, RR=0.11) and 67 cases (IR=6.36) appeared during first 7 years following Chernobyl accident (p < 0.0000001, RR=0.04). As concerns the older group (1–4 y.o.) we did not find any decrease of IR into the second (1993–1999) and third (2000–2006) 7-year periods. Actually we are working on the next time period (2007–2010) and new upgraded data will be presented. Long-term analysis of incidence of post-Chernobyl childhood acute leukemia permitted to discover the biphasic dynamics of infant's AL incidence rate. Significant increase into the first 7-year period followed by dramatic decrease between year +8 and year + 21. From radiological point of view it is relatively simpler to explain the increase into the first 7 years, because ionizing radiation is one of the few exposures for which the casual relationship with childhood leukemia has been established. Much more difficult to explain following after decrease in incidence rate of infant leukemia in Belarus. Can we speculate about the “adaptation-to-radiation” mechanisms? Over the past decades the growing body of data from cell cultures, experimental animals and humans suggests that low-dose ionizing radiation may have some beneficial (hormetic or adoptive) effect. Several epidemiological studies (India, China, Japan, USA) of a long-term low dose environmental irradiation are in favor of the hypothesis of radiation hormesis or adaptation. The carcinogenic effects of low dose radiation exposure may be restricted to children exposed in utero or in early infancy (0-12 months) during the first years after explosion. Following after dramatic decrease of IRs of infant leukemia might be explained by the developing of adaptive response to chronic low dose ionizing radiation exposure. The presented data may be one of the first clinical evidence concerning human ability of adaptation to long-term low dose radiation. Disclosures: No relevant conflicts of interest to declare.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 906
Author(s):  
Thomas Cahill ◽  
Willian Abraham da Silveira ◽  
Ludivine Renaud ◽  
Tucker Williamson ◽  
Hao Wang ◽  
...  

The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. In the gastrointestinal tract (GIT) this can lead to leaky gut syndrome, perforations and motility issues, which impact GIT functionality and affect nutritional status. While current countermeasures such as shielding from the spacecraft can attenuate harmful biological effects, they produce harmful secondary particles that contribute to radiation exposure. We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and reduced temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing and qPCR of mRNA extracted from the GIT. Pathway and network analysis were performed on the transcriptomic data to characterise the genomic signatures in radiation, torpor and torpor + radiation groups. Phenotypic analyses revealed that melatonin and reduced temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Genomic analyses indicated that low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, and cell cycle arrest. Torpor attenuated the stress response through an increase in pro-survival signals, reduced oxidative stress via the oxygen effect and detection and removal of misfolded proteins. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure.


1999 ◽  
Vol 106 (4) ◽  
pp. 954-959 ◽  
Author(s):  
Wushou P. Chang ◽  
Yi-ping Lin ◽  
Pai-tsang Hwang ◽  
Jih-Luh Tang ◽  
Jer-yuan D. Chen ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyung Cheol Kim ◽  
Hyewon Oh ◽  
Je Sung You ◽  
Yong Eun Chung

AbstractGlycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 816
Author(s):  
Ashley S. Nemec-Bakk ◽  
Sarah Niccoli ◽  
Caitlund Davidson ◽  
Danika Roy ◽  
Lisa Stoa ◽  
...  

Ionizing radiation (IR) is known to cause fetal programming, but the physiological effects of low-dose IR are not fully understood. This study examined the effect of low (50 mGy) to non-lethal (300 and 1000 mGy) radiation exposure during late gestation on cardiac metabolism and oxidative stress in adult offspring. Pregnant C57BL/6J mice were exposed to 50, 300, or 1000 mGy of gamma radiation or Sham irradiation on gestational day 15. Sixteen weeks after birth, 18F-Fluorodeoxyglucose (FDG) uptake was examined in the offspring using Positron Emission Tomography imaging. Western blot was used to determine changes in oxidative stress, antioxidants, and insulin signaling related proteins. Male and female offspring from irradiated dams had lower body weights when compared to the Sham. 1000 mGy female offspring demonstrated a significant increase in 18F-FDG uptake, glycogen content, and oxidative stress. 300 and 1000 mGy female mice exhibited increased superoxide dismutase activity, decreased glutathione peroxidase activity, and decreased reduced/oxidized glutathione ratio. We conclude that non-lethal radiation during late gestation can alter glucose uptake and increase oxidative stress in female offspring. These data provide evidence that low doses of IR during the third trimester are not harmful but higher, non-lethal doses can alter cardiac metabolism later in life and sex may have a role in fetal programming.


Author(s):  
Srikanth Nayak ◽  
Arivudai Nambi ◽  
Sathish Kumar ◽  
P Hariprakash ◽  
Pradeep Yuvaraj ◽  
...  

AbstractNumerous studies have documented the adverse effects of high-dose radiation on hearing in patients. On the other hand, radiographers are exposed to a low dose of ionizing radiation, and the effect of a low dose of radiation on hearing is quite abstruse. Therefore, the present systematic review aimed to elucidate the effect of low-dose ionizing radiation on hearing. Two authors independently carried out a comprehensive data search in three electronic databases, including PUBMED/MEDLINE, CINAHL, and SCOPUS. Eligible articles were independently assessed for quality by two authors. Cochrane Risk of Bias tool was used assess quality of the included studies. Two articles met the low-dose radiation exposure criteria given by Atomic Energy Regulatory Board (AERB) and National Council on Radiation Protection (NCRP) guidelines. Both studies observed the behavioral symptoms, pure-tone hearing sensitivity at the standard, extended high frequencies, and the middle ear functioning in low-dose radiation-exposed individuals and compared with age and gender-matched controls. One study assessed the cochlear function using transient-evoked otoacoustic emissions (TEOAE). Both studies reported that behavioral symptoms of auditory dysfunction and hearing thresholds at extended high frequencies were higher in radiation-exposed individuals than in the controls. The current systematic review concludes that the low-dose ionizing radiation may affect the hearing adversely. Nevertheless, further studies with robust research design are required to explicate the cause and effect relationship between the occupational low-dose ionizing radiation exposure and hearing.


2002 ◽  
Vol 21 (2) ◽  
pp. 85-90 ◽  
Author(s):  
L E Feinendegen

This review first summarizes experimental data on biological effects of different concentrations of ROS in mammalian cells and on their potential role in modifying cell responses to toxic agents. It then attempts to link the role of steadily produced metabolic ROS at various concentrations in mammalian cells to that of environmentally derived ROS bursts from exposure to ionizing radiation. The ROS from both sources are known to both cause biological damage and change cellular signaling, depending on their concentration at a given time. At low concentrations signaling effects of ROS appear to protect cellular survival and dominate over damage, and the reverse occurs at high ROS concentrations. Background radiation generates suprabasal ROS bursts along charged particle tracks several times a year in each nanogram of tissue, i.e., average mass of a mammalian cell. For instance, a burst of about 200 ROS occurs within less than a microsecond from low-LET irradiation such as X-rays along the track of a Compton electron (about 6 keV, ranging about 1 μm). One such track per nanogram tissue gives about 1 mGy to this mass. The number of instantaneous ROS per burst along the track of a 4-meV ¬-particle in 1 ng tissue reaches some 70000. The sizes, types and sites of these bursts, and the time intervals between them directly in and around cells appear essential for understanding low-dose and low dose-rate effects on top of effects from endogenous ROS. At background and low-dose radiation exposure, a major role of ROS bursts along particle tracks focuses on ROS-induced apoptosis of damage-carrying cells, and also on prevention and removal of DNA damage from endogenous sources by way of temporarily protective, i.e., adaptive, cellular responses. A conclusion is to consider low-dose radiation exposure as a provider of physiological mechanisms for tissue homoeostasis.


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