DNA damage and repair in patients undergoing myocardial perfusion single-photon emission computed tomography

Abstract

As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage.

Keywords: Comet assay; DNA; Myocardial perfusion imaging; Radiation.

Figure 1

Distributions of medians of comet assay descriptors: percentage of DNA in the tail, tail length and tail moment (per subject before [Pre-Exp] and after [Post-Exp] exposure to ionizing radiation).

Figure 2

Expression of DNA damage response genes using qPCR. Box plot of delta Ct values in pre-exposure and post-exposure samples, per subject. ATM Ataxia Telangiectasia Mutated. serine/threonine protein kinase, ATR Ataxia Telangiectasia and Rad3-related protein, BRCA1 Breast Cancer 1, CDKN1A Cyclin Dependent Kinase Inhibitor 1A, XPC Xeroderma Pigmentosum, Complementation Group C.