99mTc-labeled HYNIC-DAPI causes plasmid DNA damage with high efficiency

• Published in: PloS one Vol. 9; no. 8; p. e104653
• Main Authors: Kotzerke, Joerg, Punzet, Robert, Runge, Roswitha, Ferl, Sandra, Oehme, Liane, Wunderlich, Gerd, Freudenberg, Robert
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2014; Public Library of Science (PLoS)
• Subjects: Augers; Biological effects; Biology and life sciences; Damage assessment; Deoxyribonucleic acid; DNA; DNA Breaks, Single-Stranded; DNA damage; Drug dosages; Fluorescence; Gamma irradiation; Gamma rays; Gel electrophoresis; Indoles - chemistry; Iodine; Irradiation; Nuclear medicine; Organotechnetium Compounds - chemistry; Physical Sciences; Plasmids; Plasmids - chemistry; Radiation damage; Radioisotopes; Thyroid gland; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104653

(99m)Tc is the standard radionuclide used for nuclear medicine imaging. In addition to gamma irradiation, (99m)Tc emits low-energy Auger and conversion electrons that deposit their energy within nanometers of the decay site. To study the potential for DNA damage, direct DNA binding is required. Plasmid DNA enables the investigation of the unprotected interactions between molecules and DNA that result in single-strand breaks (SSBs) or double-strand breaks (DSBs); the resulting DNA fragments can be separated by gel electrophoresis and quantified by fluorescent staining. This study aimed to compare the plasmid DNA damage potential of a (99m)Tc-labeled HYNIC-DAPI compound with that of (99m)Tc pertechnetate ((99m)TcO4(-)). pUC19 plasmid DNA was irradiated for 2 or 24 hours. Direct and radical-induced DNA damage were evaluated in the presence or absence of the radical scavenger DMSO. For both compounds, an increase in applied activity enhanced plasmid DNA damage, which was evidenced by an increase in the open circular and linear DNA fractions and a reduction in the supercoiled DNA fraction. The number of SSBs elicited by 99mTc-HYNIC-DAPI (1.03) was twice that caused by (99m)TcO4(-) (0.51), and the number of DSBs increased fivefold in the (99m)Tc-HYNIC-DAPI-treated sample compared with the (99m)TcO4(-) treated sample (0.02 to 0.10). In the presence of DMSO, the numbers of SSBs and DSBs decreased to 0.03 and 0.00, respectively, in the (99m)TcO4(-) treated samples, whereas the numbers of SSBs and DSBs were slightly reduced to 0.95 and 0.06, respectively, in the (99m)Tc-HYNIC-DAPI-treated samples. These results indicated that (99m)Tc-HYNIC-DAPI induced SSBs and DSBs via a direct interaction of the (99m)Tc-labeled compound with DNA. In contrast to these results, (99m)TcO4(-) induced SSBs via radical formation, and DSBs were formed by two nearby SSBs. The biological effectiveness of (99m)Tc-HYNIC-DAPI increased by approximately 4-fold in terms of inducing SSBs and by approximately 10-fold in terms of inducing DSBs.