Effect of Low Dose Ionising Radiation on the Amount of Mitochondrial Common Deletion and D-Loop Tandem Duplication in Human Peripheral Whole Blood

doi: 10.32567/hm.2023.4.5

Absztrakt

The Hungarian Defence Forces assume a significant role in disaster prevention, including nuclear accident prevention tasks, so both the command and executive staff can stay in the higher-than-natural dose area. The current “gold standard” microscopic method aimed at determining the radiation dose suffered is the dicentric chromosome assay (DIC), although sensitive and accurate, it is very time-consuming. Monitoring changes in the amount of common deletion (CD) of mitochondrial DNA (mtDNA) and in the D-loop a tandem duplication (TD) of mtDNA may be a reliable marker of exposure to ionising radiation. This work used the PCR method to investigate how CD and TD change in human blood samples after X-ray irradiation. The CD appears to be a particularly useful marker, as its maximum is below the threshold for clinical symptoms. This work is the first to show the relationship between radiation and tandem duplication. The TD we investigated occurred
more frequently in irradiated human blood samples than native ones. During the future development of the diagnostic tool, both CD and TD are informative and would be used together in a PCR system to detect acute and cumulative irradiation. In recent years, more and more health institutions are dealing with molecular biological diagnostic work. In a disaster situation, if the laboratory capacity of the Hungarian Defence Forces would not be sufficient for this, more external laboratories can be involved for PCR measurements than for traditional microscopic work.

Kulcsszavak:

biodosimetry radiation detection deletion DNA mitochondrion

Hogyan kell idézni

Deli, G., Kulin, F., & Angyalné Pataki, Ágnes. (2024). Effect of Low Dose Ionising Radiation on the Amount of Mitochondrial Common Deletion and D-Loop Tandem Duplication in Human Peripheral Whole Blood. Hadmérnök, 18(4), 63–78. https://doi.org/10.32567/hm.2023.4.5

Hivatkozások

AHMADI, Mahboube et al. (2019): Mitochondrial Common Deletion Level in Blood: New Insight into the Effects of Age and Body Mass Index. Current Aging Science, 11(4), 250–254. Online: https://doi.org/10.2174/1874609812666190201163421

AMES, Bruve N. (1989): Endogenous DNA Damage as Related to Cancer and Aging. Mutation Research, 214(1), 41–46. Online: https://doi.org/10.1016/0027-5107(89)90196-6

ANDERSON, S. et al. (1981): Sequence and Organization of the Human Mitochondrial Genome. Nature, 290(5806), 457–465. Online: https://doi.org/10.1038/290457a0

BORGHINI, Andrea et al. (2019): Increased Mitochondrial DNA4977-bp Deletion in Catheterization Laboratory Workers with Long-Term Low-Dose Exposure to Ionizing Radiation. European Journal of Preventive Cardiology, 26(9), 976–984. Online: https://doi.org/10.1177/2047487319831495

CLAYTON, Davod A. (1991): Replication and Transcription of Vertebrate Mitochondrial DNA. Annual Review of Cell Biology, 1991(7), 453–478. Online: https://doi.org/10.1146/annurev.cb.07.110191.002321

CORRAL-DEBRINSKI, M. et al. (1992): Association of Mitochondrial DNA Damage with Aging and Coronary Atherosclerotic Heart Disease. Mutation Research, 275(3–6), 169–180. Online: https://doi.org/10.1016/0921-8734(92)90021-G

CORTOPASSI, Gino A. – ARNHEIM, Norman (1990): Detection of a Specific Mitochondrial DNA Deletion in Tissues of Older Humans. Nucleic Acids Research, 18(23), 6927–6933. Online: https://doi.org/10.1093/nar/18.23.6927

CORTOPASSI, Gino A. et al. (1992): A Pattern of Accumulation of a Somatic Deletion of Mitochondrial DNA in Aging Human Tissues. Proceedings of the National Academy of Sciences of United States of America, 89(16), 7370–7374. Online: https://doi.org/10.1073/pnas.89.16.7370

DAINIAK, Nicholas et al. (2003): The Hematologist and Radiation Casualties. Hematology. American Society of Hematology. Education Program, 2003(1), 473–496. Online: https://doi.org/10.1182/asheducation-2003.1.473

DAMAS, Joana et al. (2014): MitoBreak: The Mitochondrial DNA Breakpoints Database. Nucleic Acids Research, 42(D1), 1261–1268. Online: https://doi.org/10.1093/nar/gkt982

DELI, Gábor (2018): Cytogenetic Detection Tools for Effects of Ionizing Radiation on Human. Hadmérnök, 13(3), 179–192.

DELI, Gábor (2022): Mechanism of Action and Use of Radiomimetic Compounds. Hadmérnök, 17(1), 101–115. Online: https://doi.org/10.32567/hm.2022.1.7

DELI, Gábor (2023): Mechanism of Action and Use of Radiomimetic Compounds – Part 2. Hadmérnök, 18(2), 57–72. Online: https://doi.org/10.32567/hm.2023.2.3

FONTANA, Gabriele A. – GAHLON, Hailey L. (2020): Mechanisms of Replication and Repair in Mitochondrial DNA Deletion Formation. Nucleic Acids Research, 48(20), 11244–11258. Online: https://doi.org/10.1093/nar/gkaa804

FRAGA, C. G. et al. (1990): Oxidative Damage to DNA During Aging: 8-Hydroxy-2'-Deoxyguanosine in Rat Organ DNA and Urine. Proceedings of the National Academy of Sciences of United States of America, 87(12), 4533–4537. Online: https://doi.org/10.1073/pnas.87.12.4533

GERHARD, Glenn S. et al. (2002): Mitochondrial DNA Mutation Analysis in Human Skin Fibroblasts from Fetal, Young, and Old Donors. Mechanisms of Ageing and Development, 123(2–3), 155–166. Online: https://doi.org/10.1016/S0047-6374(01)00328-1

HARRISON, John et al. (2017): The Polonium-210 Poisoning of Mr Alexander Litvinenko. Journal of Radiological Protection, 37(1), 266–278. Online: https://doi.org/10.1088/1361-6498/aa58a7

HOFFMANN, Wolfgang – SCHMITZ-FEUERHAKE, Inge (1999): How Radiation-Specific is the Dicentric Assay? Journal of Exposure Science & Environmental Epidemiology, 9(2), 113–133. Online: https://doi.org/10.1038/sj.jea.7500008

International Atomic Energy Agency (2011): Cytogenetic Dosimetry: Applications in Preparedness for and Response to Radiation Emergencies, Emergency Preparedness and Response. Vienna: IAEA.

JESSIE, B. C. et al. (2001): Accumulation of Mitochondrial DNA Deletions in the Malignant Prostate of Patients of Different Ages. Experimental Gerontology, 37(1), 169–174. Online: https://doi.org/10.1016/S0531-5565(01)00153-X

JIANG, Min et al. (2021): The Mitochondrial Single-Stranded DNA Binding Protein is Essential for Initiation of mtDNA Replication. Science Advances, 7(27), eabf8631. Online: https://doi.org/10.1126/sciadv.abf8631

KANEKO, Natsumi et al. (2012): Mitochondrial Common Deletion Mutation and Extrinsic Skin Ageing in German and Japanese Women. Experimental Dermatology, 21(Suppl 1), 26–30. Online: https://doi.org/10.1111/j.1600-0625.2012.01499.x

KIM, Grace J. et al. (2006): A Role for Mitochondrial Dysfunction in Perpetuating Radiation-Induced Genomic Instability. Cancer Research, 66(21), 10377–10383. Online: https://doi.org/10.1158/0008-5472.CAN-05-3036

KISS Enikő et al. (2013): A sugárérzékenység vizsgálatának katasztrófavédelmi jelentősége. Hadmérnök, 8(4), 104–112.

KRISHNAN, Kim J. – BIRCH-MACHIN, Mark A. (2006): The Incidence of Both Tandem Duplications and the Common Deletion in mtDNA from Three Distinct Categories of Sun-Exposed Human Skin and in Prolonged Culture of Fibroblasts. Journal of Investigative Dermatology, 126(2), 408–415. Online: https://doi.org/10.1038/sj.jid.5700099

LIAO, Siyang et al. (2022): The Fate of Damaged Mitochondrial DNA in the Cell. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research, 1869(5), 119233. Online: https://doi.org/10.1016/j.bbamcr.2022.119233

LIVAK, Kenneth J. – Schmittgen, Thomas D. (2001): Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25(4), 402–408. Online: https://doi.org/10.1006/meth.2001.1262

LEACH, J. K. et al. (2001): Ionizing Radiation-Induced, Mitochondria-Dependent Generation of Reactive Oxygen/Nitrogen. Cancer Research, 61(10), 3894–3901.

LEE, Hsin-Chen et al. (1994a): Differential Accumulations of 4,977 bp Deletion in Mitochondrial DNA of Various Tissues in Human Ageing. Biochimica et Biophysica Acta, 1226(1), 37–43. Online: https://doi.org/10.1016/0925-4439(94)90056-6

LEE, Hsin-Chen et al. (1994b): Ageing-Associated Tandem Duplications in the D-Loop of Mitochondrial DNA of Human Muscle. FEBS Letters, 354(1), 79–83. Online: https://doi.org/10.1016/0014-5793(94)01063-3

LEE, Hsin-Chen et al. (2001): Accumulation of Mitochondrial DNA Deletions in Human Oral Tissues -- Effects of Betel Quid Chewing and Oral Cancer. Mutation Research, 493(1–2), 67–74. Online: https://doi.org/10.1016/S1383-5718(01)00160-7

PESZNYÁK, Csilla – SÁFRÁNY, Géza (2016): Sugárbiológia [Radiation Biology]. Budapest: Typotex.

PHILLIPS, Nicole R. et al. (2014): Simultaneous Quantification of Mitochondrial DNA Copy Number and Deletion Ratio: A Multiplex Real-Time PCR Assay. Scientific Reports, (4), 3887. Online: https://doi.org/10.1038/srep03887

ROGOUNOVITCH, Tatiana I. et al. (2002): Large Deletions in Mitochondrial DNA in Radiation-Associated Human Thyroid Tumors. Cancer Research, 62(23), 7031–7041.

SCHILLING-TÓTH, Boglárka et al. (2011): Analysis of the Common Deletions in the Mitochondrial DNA is a Sensitive Biomarker Detecting Direct and Non-Targeted Cellular Effects of Low Dose Ionizing Radiation. Mutation Research, 716(1–2), 33–39. Online: https://doi.org/10.1016/j.mrfmmm.2011.07.018

SCHILLING-TÓTH, Boglárka (2015): Investigation of Molecular Changes Induced by Ionizing Radiation in Normal Fibroblasts and Tumor Cells. Doctoral Thesis, Semmelweis University Doctoral School of Pathological Medicine.

SCHON, Eric A. et al. (1989): A Direct Repeat is a Hotspot for Large-Scale Deletion of Human Mitochondrial DNA. Science, 244(4902), 346–349. Online: https://doi.org/10.1126/science.2711184

SCHÜLE, Simone et al. (2022): Identifying Radiation Responsive Exon-Regions of Genes Often Used for Biodosimetry and Acute Radiation Syndrome Prediction. Scientific Reports, 12(1), 9545. Online: https://doi.org/10.1038/s41598-022-13577-4

SHOFFNER, J. M. et al. (1989): Spontaneous Kearns-Sayre/Chronic External Ophthalmoplegia Plus Syndrome Associated with a Mitochondrial DNA Deletion: A Slip-Replication Model and Metabolic Therapy. Proceedings of the National Academy of Sciences of United States of America, 86(20), 7952–7956. Online: https://doi.org/10.1073/pnas.86.20.7952

SIGURDSON, Alice J. et al. (2008): International Study of Factors Affecting Human Chromosome Translocations. Mutation Research, 652(2), 112–121. Online: https://doi.org/10.1016/j.mrgentox.2008.01.005

VOISIN, Philippe (2015): Standards in Biological Dosimetry: A Requirement to Perform an Appropriate Dose Assessment. Mutation Research, 793, 115–122. Online: https://doi.org/10.1016/j.mrgentox.2015.06.012

WALLACE, Douglas C. (1992): Mitochondrial Genetics: A Paradigm for Aging and Degenerative Diseases? Science, 256(5057), 628–632. Online: https://doi.org/10.1126/science.1533953

WANG, Ping et al. (2013): Mitochondria DNA 4977 bp Common Deletion in Peripheral Whole Blood from Healthy Donors. Biomedical and Environmental Sciences, 26(12), 990–993. Online: https://doi.org/10.3967/bes2013.035

WANGA, Lu et al. (2007): Analysis of Common Deletion (CD) and a Novel Deletion of Mitochondrial DNA Induced by Ionizing Radiation. International Journal of Radiation Biology, 83(7), 433–442. Online: https://doi.org/10.1080/09553000701370878

WHITEHOUSE, C. A. et al. (2005): Translocation Yields in Peripheral Blood Lymphocytes from Control Populations. International Journal of Radiation Biology, 81(2), 139–145. Online: https://doi.org/10.1080/09553000500103082

YEN, Tzu-Chen et al. (1991): Ageing-Associated 5 kb Deletion in Human Liver Mitochondrial DNA. Biochemical and Biophysical Research Communications, 178(1), 124–131. Online: https://doi.org/10.1016/0006-291X(91)91788-E