DNA Damage and Repair in Patients Undergoing Myocardial Perfusion Single-photon Emission Computed Tomography

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jun 6

PMID 38844507

Authors

Andrea De Lorenzo

Maria Clara Dos Santos Fernandes

Francisco Romeiro

Anna Paula Arpini

Glauber Monteiro Dias

Affiliations

Soon will be listed here.

Abstract

As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage.

References

Hartmann A, Speit G . Genotoxic effects of chemicals in the single cell gel (SCG) test with human blood cells in relation to the induction of sister-chromatid exchanges (SCE). Mutat Res. 1995; 346(1):49-56. DOI: 10.1016/0165-7992(95)90068-3. View

Hendel R, Berman D, Di Carli M, Heidenreich P, Henkin R, Pellikka P . ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging: A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the.... J Am Coll Cardiol. 2009; 53(23):2201-29. DOI: 10.1016/j.jacc.2009.02.013. View

Azzam E, Jay-Gerin J, Pain D . Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett. 2011; 327(1-2):48-60. PMC: 3980444. DOI: 10.1016/j.canlet.2011.12.012. View

Wu J, Lu L, Yu X . The role of BRCA1 in DNA damage response. Protein Cell. 2011; 1(2):117-23. PMC: 3078634. DOI: 10.1007/s13238-010-0010-5. View

Arpini A, De Lorenzo A, Moritz A, Passarelli Pereira J, Monteiro Dias G . Evaluation of DNA damage induced by ionizing radiation from myocardial perfusion imaging: a pilot study. BMC Cardiovasc Disord. 2022; 22(1):394. PMC: 9441099. DOI: 10.1186/s12872-022-02839-8. View

Schipler A, Iliakis G . DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice. Nucleic Acids Res. 2013; 41(16):7589-605. PMC: 3763544. DOI: 10.1093/nar/gkt556. View

Badie C, Dziwura S, Raffy C, Tsigani T, Alsbeih G, Moody J . Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment. Br J Cancer. 2008; 98(11):1845-51. PMC: 2410125. DOI: 10.1038/sj.bjc.6604381. View

Einstein A . Effects of radiation exposure from cardiac imaging: how good are the data?. J Am Coll Cardiol. 2012; 59(6):553-65. PMC: 3272627. DOI: 10.1016/j.jacc.2011.08.079. View

Varol S, Oktem F, Kocyigit A, Dogan Demir A, Karatas E, Aydin M . The impact of Technetium-99m dimercapto-succinic acid scintigraphy on DNA damage and oxidative stress in children. Int J Clin Pract. 2021; 75(11):e14810. DOI: 10.1111/ijcp.14810. View

10.

Lee W, Nguyen P, Hu S, Liang G, Ong S, Han L . Variable activation of the DNA damage response pathways in patients undergoing single-photon emission computed tomography myocardial perfusion imaging. Circ Cardiovasc Imaging. 2015; 8(2):e002851. PMC: 4354894. DOI: 10.1161/CIRCIMAGING.114.002851. View

11.

Rief M, Hartmann L, Geisel D, Richter F, Brenner W, Dewey M . DNA double-strand breaks in blood lymphocytes induced by two-day Tc-MIBI myocardial perfusion scintigraphy. Eur Radiol. 2018; 28(7):3075-3081. DOI: 10.1007/s00330-017-5239-4. View

12.

Al Nasrallah N, Wiese B, Sears C . Xeroderma Pigmentosum Complementation Group C (XPC): Emerging Roles in Non-Dermatologic Malignancies. Front Oncol. 2022; 12:846965. PMC: 9069926. DOI: 10.3389/fonc.2022.846965. View

13.

Mu H, Geacintov N, Broyde S, Yeo J, Scharer O . Molecular basis for damage recognition and verification by XPC-RAD23B and TFIIH in nucleotide excision repair. DNA Repair (Amst). 2018; 71:33-42. PMC: 6340764. DOI: 10.1016/j.dnarep.2018.08.005. View

14.

Shirazi M, Shabestani-Monfared A, Shahidi M, Amiri M, Abedi S, Borzoueisileh S . Radio-adaptive Response in Myocardial Perfusion Imaging Induced by Technetium-99m. Indian J Nucl Med. 2017; 32(1):7-10. PMC: 5317080. DOI: 10.4103/0972-3919.198446. View

15.

. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007; 37(2-4):1-332. DOI: 10.1016/j.icrp.2007.10.003. View

16.

Welcsh P, King M . BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum Mol Genet. 2001; 10(7):705-13. DOI: 10.1093/hmg/10.7.705. View

17.

Khanna K, Jackson S . DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001; 27(3):247-54. DOI: 10.1038/85798. View

18.

Chen J, Einstein A, Fazel R, Krumholz H, Wang Y, Ross J . Cumulative exposure to ionizing radiation from diagnostic and therapeutic cardiac imaging procedures: a population-based analysis. J Am Coll Cardiol. 2010; 56(9):702-11. PMC: 2952402. DOI: 10.1016/j.jacc.2010.05.014. View

19.

Hartwell L, Weinert T . Checkpoints: controls that ensure the order of cell cycle events. Science. 1989; 246(4930):629-34. DOI: 10.1126/science.2683079. View

20.

Yan Y, Black C, Cao P, Haferbier J, Kolb R, Spieker R . Gamma-irradiation-induced DNA damage checkpoint activation involves feedback regulation between extracellular signal-regulated kinase 1/2 and BRCA1. Cancer Res. 2008; 68(13):5113-21. PMC: 3674789. DOI: 10.1158/0008-5472.CAN-07-5818. View