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

2017 ◽  
Vol 58 (3) ◽  
pp. 329-340 ◽  
Author(s):  
Ji-Hye Yim ◽  
Jung Mi Yun ◽  
Ji Young Kim ◽  
In Kyung Lee ◽  
Seon Young Nam ◽  
...  

Abstract 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.

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.


Author(s):  
M. Alcantara ◽  
D. Paunesku ◽  
T. Paunesku ◽  
A. Wahl ◽  
Y. Kataoka ◽  
...  

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi13-vi14
Author(s):  
William Breen ◽  
S Keith Anderson ◽  
Xiomara Carrero ◽  
Paul Brown ◽  
Karla Ballman ◽  
...  

Abstract PURPOSE To provide a final update on oncologic and cognitive outcomes of high dose versus low dose radiation for low-grade glioma. METHODS Between 1986 and 1994, 203 patients with supratentorial low grade glioma were randomized to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection. Histologic subtype was oligodendroglioma (71%) or astrocytoma (29%). Primary outcome was overall survival (OS). Cognitive status was followed using Folstein Mini-Mental State Examination (MMSE). RESULTS For the entire cohort of 203 patients, median OS was 8.4 years (95% CI: 7.2 – 10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3 – 6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve OS (15-yr OS: 22.4% vs. 24.9%, log rank p=0.978) or PFS (15-yr PFS: 15.2% vs. 9.5%, p=0.7142). OS was significantly better for patients with pre-operative tumor diameter < 5 cm (15-yr OS: 39.4% vs. 15.2%, p< 0.001), baseline MMSE > 27 (15-yr OS: 27.3% vs. 9.8%, p=0.001), and for patients who underwent gross total resection (GTR) (15-yr OS: 39.3% GTR vs. 16.4% subtotal resection vs. 24.5% biopsy only, p=0.0119). PFS was improved for patients with oligodendroglioma versus astrocytoma (15-yr PFS: 13.8% vs. 8.6%, p=0.0221). PFS was also improved for patients with pre-operative tumor diameter < 5 cm, patients who had GTR, and patients with baseline MMSE > 27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years. CONCLUSIONS Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Minimal late decline in cognitive function after radiation was seen by MMSE. SUPPORT: U10CA180821,U10CA180882. https://acknowledgments.alliancefound.org


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.


2013 ◽  
Vol 180 (4) ◽  
pp. 376 ◽  
Author(s):  
M. D. Lawrence ◽  
R. J. Ormsby ◽  
B. J. Blyth ◽  
E. Bezak ◽  
G. England ◽  
...  

2020 ◽  
Vol 22 (6) ◽  
pp. 830-837 ◽  
Author(s):  
William G Breen ◽  
S Keith Anderson ◽  
Xiomara W Carrero ◽  
Paul D Brown ◽  
Karla V Ballman ◽  
...  

Abstract Background The optimal radiation dose for adult supratentorial low-grade glioma is unknown. The aim of this study was to provide a final update on oncologic and cognitive outcomes of high-dose versus low-dose radiation for low-grade glioma. Methods Between 1986 and 1994, 203 patients with supratentorial low-grade glioma were randomized (1:1) to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection. Results For all patients, median overall survival (OS) was 8.4 years (95% CI: 7.2–10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3–6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve 15-year OS (22.4%) versus low-dose radiation (24.9%, log-rank P = 0.978) or 15-year PFS (high dose, 15.2% vs low dose, 9.5%; P = 0.7142). OS was significantly better for patients with preoperative tumor diameter &lt;5 cm and baseline Mini-Mental State Examination (MMSE) &gt;27 and who underwent gross total resection. PFS was improved for patients with oligodendroglioma versus astrocytoma, preoperative tumor diameter &lt;5 cm, patients who had gross total resection, and patients with baseline MMSE &gt;27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years. Conclusions Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Cognitive function appeared to be stable after radiation as measured by MMSE.


2017 ◽  
Vol 51 (4) ◽  
pp. 369-377 ◽  
Author(s):  
Igor Piotrowski ◽  
Katarzyna Kulcenty ◽  
Wiktoria Maria Suchorska ◽  
Agnieszka Skrobała ◽  
Małgorzata Skórska ◽  
...  

AbstractBackgroundAlthough the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.ConclusionsUnderstanding the molecular mechanisms of response to low dose radiation is crucial for the proper evaluation of risks and benefits that stem from these exposures and should be considered in the radiotherapy treatment planning and in determining the allowed occupational exposures.


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