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      Assessment of Adaptive Response of Gamma Radiation in the Operating Room Personnel Exposed to Anesthetic Gases by Measuring the Relative Gene Expression Changes Ku80, Ligase1 and P53

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          Abstract

          Background:

          Some operating room personnel are occupationally exposed to genotoxic agents such as anesthetic gases and ionizing radiation. Adaptive response, as a defense mechanism, will occur when cells become exposed to a low dose of factors harming DNA (priming dose), which in the subsequent exposure to higher dose of those factors (challenging dose), show more resistance and sensibility.

          Objective:

          The aim of this study was to investigate adaptive response or synergy of ionizing radiation in the operating room personnel exposed to anesthetic gases by evaluation of the relative gene expression changes of effective genes for DNA repair such as Ku80, Ligase1 and P53.

          Material and Methods:

          In this case-control study, 20 operating room personnel and 20 nurses (who were not present in the operating room) as controls were studied. Venous blood samples were drawn from participants. In order to evaluate the adaptive response, a challenging dose of 2Gy gamma radiation was applied to blood samples. Moreover, RNA extraction and cDNA synthesis were performed. Gene expression level was studied by RT-qPCR and compared with the control group.

          Results:

          Ligase1 and P53 expression in the operating room personnel was significantly higher than that of the control group before irradiation (P˂0.001). Statistically, there was no significant difference in the Ku80 and P53 expression in the operating room personnel before and after irradiation.

          Conclusion:

          Given the findings of this study, exposure to challenging dose of gamma radiation can induce adaptive response in expression of Ku80 and P53 genes in operating room personnel.

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          Most cited references25

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          Differential responses of stress genes to low dose-rate gamma irradiation.

          In the past, most mechanistic studies of ionizing radiation response have employed very large doses, then extrapolated the results down to doses relevant to human exposure. It is becoming increasingly apparent, however, that this does not give an accurate or complete picture of the effects of most environmental exposures, which tend to be of low dose and protracted over time. We have initiated direct studies of low dose exposures, and using the relatively responsive ML-1 cell line, have shown that changes in gene expression can be triggered by doses of gamma-rays of 10 cGy and less in human cells. We have now extended these studies to investigate the effects on gene induction of reducing the rate of irradiation. In the ML-1 human myeloid leukemia cell line, we have found that reducing the dose rate over three orders of magnitude results in some protection against the induction of apoptosis, but still causes linear induction of the p53-regulated genes CDKN1A, GADD45A, and MDM2 between 2 and 50 cGy. Reducing the rate of exposure reduces the magnitude of induction of CDKN1A and GADD45A, but not the magnitude or duration of cell cycle delay. In contrast, MDM2 is induced to the same extent regardless of the rate of dose delivery. Microarray analysis has identified additional low dose-rate-inducible genes, and indicates the existence of two general classes of low dose-rate responders in ML-1. One group of genes is induced in a dose rate-dependent fashion, similar to GADD45A and CDKN1A. Functional annotation of this gene cluster indicates a preponderance of genes with known roles in apoptosis regulation. Similarly, a group of genes with dose rate-independent induction, such as seen for MDM2, was also identified. The majority of genes in this group are involved in cell cycle regulation. This apparent differential regulation of stress signaling pathways and outcomes in response to protracted radiation exposure has implications for carcinogenesis and risk assessment, and could not have been predicted from classical high dose studies.
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            Overview of Biological, Epidemiological, and Clinical Evidence of Radiation Hormesis

            The effects of low-dose radiation are being increasingly investigated in biological, epidemiological, and clinical studies. Many recent studies have indicated the beneficial effects of low doses of radiation, whereas some studies have suggested harmful effects even at low doses. This review article introduces various studies reporting both the beneficial and harmful effects of low-dose radiation, with a critique on the extent to which respective studies are reliable. Epidemiological studies are inherently associated with large biases, and it should be evaluated whether the observed differences are due to radiation or other confounding factors. On the other hand, well-controlled laboratory studies may be more appropriate to evaluate the effects of low-dose radiation. Since the number of such laboratory studies is steadily increasing, it will be concluded in the near future whether low-dose radiation is harmful or beneficial and whether the linear-no-threshold (LNT) theory is appropriate. Many recent biological studies have suggested the induction of biopositive responses such as increases in immunity and antioxidants by low-dose radiation. Based on recent as well as classical studies, the LNT theory may be out of date, and low-dose radiation may have beneficial effects depending on the conditions; otherwise, it may have no effects.
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              Adaptive response: some underlying mechanisms and open questions

              Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection, e.g. of astronauts during long-term space flights. In this mini-review we discuss some open questions and the probable underlying mechanisms involved in adaptive response: the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses - DNA repair systems, induction of proteins synthesis, enhanced detoxification of free radicals and antioxidant production.
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                Author and article information

                Journal
                J Biomed Phys Eng
                J Biomed Phys Eng
                Journal of Biomedical Physics & Engineering
                Shiraz University of Medical Sciences (Iran )
                2251-7200
                April 2020
                01 April 2020
                : 10
                : 2
                : 225-234
                Affiliations
                [1 ] MSc, Department of Radiology, School of Paramedicine, Shiraz University of Medical Sciences, Shiraz, Iran
                [2 ] MSc, Department of Radiology, Hospital Imam Hussein Orzouieh, Kerman University of Medical Sciences, Kerman, Iran
                [3 ] PhD, Ionizing and Non-ionizing radiation protection research center, School of Paramedicine, Shiraz University of Medical, Sciences, Shiraz, Iran
                [4 ] PhD, Department of Radiology, School of Paramedicine, Shiraz University of Medical Sciences, Shiraz, Iran
                [5 ] PhD Student, Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
                [6 ] PhD, Occupational Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
                [7 ] PhD, Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedicine, Shiraz University of Medical Sciences, Shiraz, Iran
                Author notes
                *Corresponding author: R. Fardid; Department of Radiology, School of Paramedicine, Shiraz University of Medical Sciences, Shiraz, Iran. Email: rfardid@ 123456sums.ac.ir
                Article
                JBPE-10-2
                10.31661/jbpe.v0i0.1273
                7166212
                c480b2ec-e0bc-437a-8054-e468e81c09f3
                Copyright: © Journal of Biomedical Physics and Engineering

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 Unported License, ( http://creativecommons.org/licenses/by-nc/4.0/ ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 November 2019
                : 9 October 2019
                Categories
                Original Article

                adaptive response, ionizing radiation, anesthetic gases, operating room personnel, occupational exposure, dna repair, gene expression, rt-qpcr

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