Abstract 18726: Single Cell Expression Profiling Reveals Up-Regulation of Radiation Sensitive Genes After Cardiac Computed Tomographic Angiography

Abstract

Introduction: High dose radiation activates radiation sensitive genes involved in the DNA damage response pathway, which is responsible for tumor suppression. Whether low dose radiation from medical imaging tests, such as cardiac computed tomographic angiography (CTA), changes the expression of these genes is unknown.

Hypothesis: We hypothesize that low dose radiation alters the gene expression of 3 genes involved in tumor suppression: 1) MDM2 (a negative regulator of p53-induced cell cycle arrest and apoptosis), 2) BAX (a mediator of p53-induced apoptosis), and 3) DDB2 (a mediator of DNA repair).

Methods: To determine the optimal time point for collection of blood in vivo, we performed an in vitro study. Blood from healthy volunteers (n=4) received either irradiation with a single dose of 25 mGy or 5,000 mGy, or received sham-irradiation. Whole blood was maintained at 37° for 6, 12, 24, and 38 hours following irradiation. Blood was collected from adult patients immediately before and 24 hours after CTA (n=10) or echocardiography (n=5). After separation of lymphocytes, gene expression was analyzed by single cell polymerase chain reaction.

Results: The in vitro study showed significant up-regulation of MDM2, BAX, and DDB2 after low and high dose irradiation compared with sham-irradiated controls (Figure 1A, B, C). Similarly, up-regulation of these genes was noted in patients undergoing CTA (3-15 mSv) for various indications but not in patients undergoing echocardiography (Figure 1D). Of note, only 50% of patients had changes in gene expression.

Conclusions: Low dose radiation from CTA alters the expression of genes involved in regulating tumor suppression. These findings, however, are seen in only 50% of patients. Further investigation is needed to determine how to identify these “radiosensitive” patients.