scholarly journals MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kuei-Fang Lee ◽  
Yi-Cheng Chen ◽  
Paul Wei-Che Hsu ◽  
Ingrid Y. Liu ◽  
Lawrence Shih-Hsin Wu

Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE) is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs) have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cells. By utilizing publicly available microRNA knowledge bases and performing cross validations with our previous gene expression profiling under the same radiation condition, we identified various miRNA-gene interactions specific to different doses of radiation treatment, providing new insights for the molecular underpinnings of radiation injury.

2004 ◽  
Vol 23 (2) ◽  
pp. 61-65 ◽  
Author(s):  
Edouard I Azzam ◽  
John B Little

A multitude of biological effects observed over the past two decades in various in vivo and in vitro cell culture experiments have indicated that low dose/low fluence ionizing radiation has significantly different biological responses than high dose radiation. Exposure of cell populations to very low fluences of particles or incorporated radionuclides results in significant biological effects occurring in both the irradiated and nonirradiated cells in the population. Cells recipient of growth medium from irradiated cultures can also respond to the radiation exposure. This phenomenon, termed the ‘bystander response’, has been postulated to impact both the estimation of risks of exposure to ionizing radiation and radiotherapy. Amplification of radiation-induced cyto-toxic and genotoxic effects by the bystander effect is in contrast to the observations of adaptive responses, which are generally induced following exposure to low dose, low linear energy transfer radiation and which tend to attenuate radiation-induced damage. In this article, the evidence for existence of radiation-induced bystander effects and our current knowledge of the biochemical and molecular events involved in mediating these effects are described. Potential similarities between factors that mediate the radiation-induced bystander and adaptive responses are highlighted.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3843
Author(s):  
Jeffrey R. Whiteaker ◽  
Tao Wang ◽  
Lei Zhao ◽  
Regine M. Schoenherr ◽  
Jacob J. Kennedy ◽  
...  

The ATM serine/threonine kinase (HGNC: ATM) is involved in initiation of repair of DNA double-stranded breaks, and ATM inhibitors are currently being tested as anti-cancer agents in clinical trials, where pharmacodynamic (PD) assays are crucial to help guide dose and scheduling and support mechanism of action studies. To identify and quantify PD biomarkers of ATM inhibition, we developed and analytically validated a 51-plex assay (DDR-2) quantifying protein expression and DNA damage-responsive phosphorylation. The median lower limit of quantification was 1.28 fmol, the linear range was over 3 orders of magnitude, the median inter-assay variability was 11% CV, and 86% of peptides were stable for storage prior to analysis. Use of the assay was demonstrated to quantify signaling following ionizing radiation-induced DNA damage in both immortalized lymphoblast cell lines and primary human peripheral blood mononuclear cells, identifying PD biomarkers for ATM inhibition to support preclinical and clinical studies.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Kuei-Fang Lee ◽  
Julia Tzu-Ya Weng ◽  
Paul Wei-Che Hsu ◽  
Yu-Hsiang Chi ◽  
Ching-Kai Chen ◽  
...  

Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.


2018 ◽  
Vol 10 (8) ◽  
pp. 2776 ◽  
Author(s):  
Cristian Vergallo ◽  
Luciana Dini

Moderate static magnetic fields (SMFs) are generated from sources such as new-generation electric trams and trains, electric arc welding, and magnetic resonance imaging (MRI) devices, as well as during the industrial production of aluminium, while extremely low frequency pulsed magnetic fields (ELF-PMFs) are produced by house power installations, household appliances, and high voltages transmission lines. Moderate SMFs and ELF-PMFs with magnetic flux densities (B) in the range of 1–60 mT and frequencies (f) up to 50 Hz are common MF exposure sources for the population. Even though humans are continually exposed to these MFs, to date no definitive endpoint has been drawn about their safety. In this review, the state of knowledge about the biological effects induced by these MFs on different cell types will be addressed. In our own observation, the putative modulation of Ca2+/H+ and Na+/H+ plasma membrane antiporters of human peripheral blood lymphocytes (PBLs) was found to occur after a 24 h exposure to a 6 mT SMF, and the bystander effect observed on U937 cells cultivated for up to 6 h in the conditioned medium harvested from human PBLs previously exposed for 24 h to the same MF (secondary necrosis induction) will be also herein discussed.


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