Abstract 17674: Cell Damage and Even Death Detected in Peripheral T-Lymphocytes in Patients Undergoing Cardiac Computed Tomographic Angiography
Background: It is well known that radiation can cause cell damage and even cell death at high doses. Whether a similar albeit less pronounced effect exists at low dose remains unclear.
Objective: The purpose of this study is to determine whether low dose radiation from cardiac computed tomographic angiography (CCTA) is associated with cellular damage.
Methods: Blood was collected from 56 adult patients immediately before and after CCTA. Changes in protein phosphorylation and gene expression were analyzed by quantitative flow cytometry and single cell gene expression profiling, respectively. The presence of cell death was analyzed by flow cytometry in a subset of patients (n=25).
Results: Activation of multiple proteins and genes were detected by quantitative flow cytometry and single cell expression profiling after exposure to ≥25 mSv of radiation in vitro. Similarly, blood collected from patients undergoing CCTA showed increased protein (i.e., H2AX, p53, and ATM) and gene (i.e., p53, BAX, MDM2, CDK4, ATF6, and DDB2) activation. A linear-dose response relationship was found in phosphorylated ATM, CDK4 and DDB2 in vivo. Sixty-eight percent (n=17/25; average % cell death 1.4%±0.9%; n=100,000 events) of patients had evidence of T-lymphocyte death after exposure. Patients with DNA damage (i.e. affected patients) as indicated by phosphorylation of H2AX, ATM and/or p53 had more cell death than those without DNA damage (3.7 vs. 1.09 fold, p=0.005) (Figure 1A). Patients with increased cell death were exposed to higher amounts of radiation (38.5 ± 18.4 mSv vs. 15.1 ± 13.4 mSv, p=0.004). With the exception of two patients, most patients who had significant cell death (i.e., >2 fold) had exposure to at least 20 mSv of radiation (Figure 1B).
Conclusion: Radiation exposure from CCTA activates multiple proteins and genes involved in the DNA damage response pathway. Cell death was detected in over half of the patients although the magnitude was small.
Author Disclosures: P. Nguyen: None. W. Lee: None. W. Hong: None. S. Hu: None. S. Ong: None. J. Churko: None. C. Chan: None. J. Wang: None. M.T. Longaker: None. M. Hlatky: None. D. Fleischmann: None. J.C. Wu: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.