An evaluation of DNA double strand break formation and excreted guanine species post whole body PET/CT procedure

Abstract

Ionizing radiation-induced oxidation and formation of deoxyribonucleic acid (DNA) double strand breaks (DSBs) are considered the exemplar of genetic lesions. Guanine bases are most prone to be oxidized when DNA and Ribonucleic acid (RNA) are damaged. The repair processes that are initiated to correct this damage release multiple oxidized guanine species into the urine. Hence, the excretion of guanine species can be related with the total repair process. Our study quantified the total DSBs formation and the amount of guanine species in urine to understand the DNA break and repair process after whole body (WB) exposure to 18F-FDG positron emission tomography/computed tomography (PET/CT). A total of 37 human participants were included with control and test groups and the average radiation dose was 27.50 ± 2.91 mSv. γ-H2AX foci assay in the collected blood samples was performed to assess the DSBs, and excreted guanine species in urine were analyzed by a competitive ELISA method. We observed a significant increase of DNA damage that correlated well with the increasing dose (p-value 0.009) and body weight (p-value 0.05). In the test group, excreted guanine species in urine sample significantly increased (from 24.29 ± 5.82 to 33.66 ± 7.20 mg/mmol creatinine). A minimum (r2 = 0.0488) correlation was observed between DSBs formation and excreted guanine species. A significant difference of DNA damage and 8-OHdG formation was seen in the test group compared to controls. Larger population studies are needed to confirm these observations, describe the fine-scale timing of changes in the biomarker levels after exposure, and further clarify any potential risks to patients from PET/CT procedures.