title: Variable activation of the DNA damage response pathways in patients undergoing single-photon emission computed tomography myocardial perfusion imaging.
abstract: BACKGROUND
  Although single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) has improved the diagnosis and risk stratification of patients with suspected coronary artery disease, it remains a primary source of low-dose radiation exposure for cardiac patients. To determine the biological effects of low-dose radiation from SPECT MPI, we measured the activation of the DNA damage response pathways using quantitative flow cytometry and single-cell gene expression profiling.
  
  
  RESULTS
  Blood samples were collected from patients before and after SPECT MPI (n=63). Overall, analysis of all recruited patients showed no marked differences in the phosphorylation of proteins (H2AX, protein 53, and ataxia telangiectasia mutated) after SPECT. The majority of patients also had either downregulated or unchanged expression in DNA damage response genes at both 24 and 48 hours post-SPECT. Interestingly, a small subset of patients with increased phosphorylation had significant upregulation of genes associated with DNA damage, whereas those with no changes in phosphorylation had significant downregulation or no difference, suggesting that some patients may potentially be more sensitive to low-dose radiation exposure.
  
  
  CONCLUSIONS
  Our findings showed that SPECT MPI resulted in a variable activation of the DNA damage response pathways. Although only a small subset of patients had increased protein phosphorylation and elevated gene expression postimaging, continued care should be taken to reduce radiation exposure to both the patients and operators.
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA.|Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA.|Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.|Veterans Administration Palo Alto, Palo Alto, CA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA.|Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.|Veterans Administration Palo Alto, Palo Alto, CA.
authors.forename: Grace
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA.|Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.
authors.forename: Sang-Ging
authors.initials: SG
authors.lastname: Ong
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA.|Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.
authors.forename: Leng
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Sanchez-Freire
authors.affiliation: Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lee
authors.affiliation: Veterans Administration Palo Alto, Palo Alto, CA.
authors.forename: Minal
authors.initials: M
authors.lastname: Vasanawala
authors.affiliation: Veterans Administration Palo Alto, Palo Alto, CA.
authors.forename: George
authors.initials: G
authors.lastname: Segall
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA.|Department of Radiology, Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004249:DNA Damage / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000528:radiation effects; D006657:Histones / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000009:adverse effects* / Q000379:methods; D010766:Phosphorylation; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000097:blood; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000097:blood / Q000209:etiology* / Q000235:genetics; D019275:Radiopharmaceuticals / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; C468783:H2AX protein, human; D006657:Histones; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: DNA damage; gene expression; single-photon emission computed tomography