title: Assessment of the Radiation Effects of Cardiac CT Angiography Using Protein and Genetic Biomarkers.
abstract: OBJECTIVE
  The purpose of this study was to evaluate whether radiation exposure from cardiac computed tomographic angiography (CTA) is associated with deoxyribonucleic acid (DNA) damage and whether damage leads to programmed cell death and activation of genes involved in apoptosis and DNA repair.
  
  
  BACKGROUND
  Exposure to radiation from medical imaging has become a public health concern, but whether it causes significant cell damage remains unclear.
  
  
  METHODS
  We conducted a prospective cohort study in 67 patients undergoing cardiac CTA between January 2012 and December 2013 in 2 U.S. medical centers. Median blood radiation exposure was estimated using phantom dosimetry. Biomarkers of DNA damage and apoptosis were measured by flow cytometry, whole genome sequencing, and single cell polymerase chain reaction.
  
  
  RESULTS
  The median dose length product was 1,535.3 mGy·cm (969.7 to 2,674.0 mGy·cm). The median radiation dose to the blood was 29.8 mSv (18.8 to 48.8 mSv). Median DNA damage increased 3.39% (1.29% to 8.04%, p < 0.0001) and median apoptosis increased 3.1-fold (interquartile range [IQR]: 1.4- to 5.1-fold, p < 0.0001) post-radiation. Whole genome sequencing revealed changes in the expression of 39 transcription factors involved in the regulation of apoptosis, cell cycle, and DNA repair. Genes involved in mediating apoptosis and DNA repair were significantly changed post-radiation, including DDB2 (1.9-fold [IQR: 1.5- to 3.0-fold], p < 0.001), XRCC4 (3.0-fold [IQR: 1.1- to 5.4-fold], p = 0.005), and BAX (1.6-fold [IQR: 0.9- to 2.6-fold], p < 0.001). Exposure to radiation was associated with DNA damage (odds ratio [OR]: 1.8 [1.2 to 2.6], p = 0.003). DNA damage was associated with apoptosis (OR: 1.9 [1.2 to 5.1], p < 0.0001) and gene activation (OR: 2.8 [1.2 to 6.2], p = 0.002).
  
  
  CONCLUSIONS
  Patients exposed to >7.5 mSv of radiation from cardiac CTA had evidence of DNA damage, which was associated with programmed cell death and activation of genes involved in apoptosis and DNA repair.
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Veterans Administration Palo Alto, Palo Alto, California; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California. Electronic address: pknguyen@stanford.edu.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Nguyen
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California.
authors.forename: Yong Fuga
authors.initials: YF
authors.lastname: Li
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California.
authors.forename: Wan Xing
authors.initials: WX
authors.lastname: Hong
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California.
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Grace
authors.initials: G
authors.lastname: Liang
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Ivy
authors.initials: I
authors.lastname: Nguyen
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California.
authors.forename: Sang-Ging
authors.initials: SG
authors.lastname: Ong
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California.
authors.forename: Jared
authors.initials: J
authors.lastname: Churko
authors.affiliation: Environmental Health and Safety, Stanford University School of Medicine, Stanford, California.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California.
authors.forename: Russ B
authors.initials: RB
authors.lastname: Altman
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California.
authors.forename: Dominik
authors.initials: D
authors.lastname: Fleischmann
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California. Electronic address: joewu@stanford.edu.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D015331:Cohort Studies; D017023:Coronary Angiography / Q000009:adverse effects*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006321:Heart / Q000528:radiation effects*; D006657:Histones / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019047:Phantoms, Imaging; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D014057:Tomography, X-Ray Computed / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D017304:Annexin A5; D015415:Biomarkers; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; C478985:PDRG1 protein, human; D051028:bcl-2-Associated X Protein; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: CT/MRI; gene expression; gene regulation; imaging