Assessment of the radiation effects of cardiac CT angiography using protein and genetic biomarkers

Patricia K. Nguyen, Won Hee Lee, Yong Fuga Li, Wan Xing Hong, Shijun Hu, Charles Chan, Grace Liang, Ivy Nguyen, Sang Ging Ong, Jared Churko, Jia Wang, Russ B. Altman, Dominik Fleischmann, Joseph C. Wu

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Objectives 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.

Original languageEnglish (US)
Pages (from-to)873-884
Number of pages12
JournalJACC: Cardiovascular Imaging
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

Keywords

  • CT/MRI
  • gene expression
  • gene regulation
  • imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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    Nguyen, P. K., Lee, W. H., Li, Y. F., Hong, W. X., Hu, S., Chan, C., Liang, G., Nguyen, I., Ong, S. G., Churko, J., Wang, J., Altman, R. B., Fleischmann, D., & Wu, J. C. (2015). Assessment of the radiation effects of cardiac CT angiography using protein and genetic biomarkers. JACC: Cardiovascular Imaging, 8(8), 873-884. https://doi.org/10.1016/j.jcmg.2015.04.016