TY - JOUR
T1 - Assessment of the radiation effects of cardiac CT angiography using protein and genetic biomarkers
AU - Nguyen, Patricia K.
AU - Lee, Won Hee
AU - Li, Yong Fuga
AU - Hong, Wan Xing
AU - Hu, Shijun
AU - Chan, Charles
AU - Liang, Grace
AU - Nguyen, Ivy
AU - Ong, Sang Ging
AU - Churko, Jared
AU - Wang, Jia
AU - Altman, Russ B.
AU - Fleischmann, Dominik
AU - Wu, Joseph C.
N1 - Funding Information:
This work was supported by the American Heart Association (10SDG4280129), National Institutes of Health (HL093172 and HL09551), and Stanford Cardiovascular Institute. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Nguyen, Lee, and Li contributed equally to this work.
Publisher Copyright:
© 2015 American College of Cardiology Foundation.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
KW - CT/MRI
KW - gene expression
KW - gene regulation
KW - imaging
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U2 - 10.1016/j.jcmg.2015.04.016
DO - 10.1016/j.jcmg.2015.04.016
M3 - Article
C2 - 26210695
AN - SCOPUS:84939494928
SN - 1936-878X
VL - 8
SP - 873
EP - 884
JO - JACC: Cardiovascular Imaging
JF - JACC: Cardiovascular Imaging
IS - 8
ER -