Molecular dosimetry of Tc-99m-and I-125-induced {center_dot}OH radicals using a DNA-conjugated fluorescent molecule
- Harvard Medical School, Boston, MA (United States); and others
Potential risks associated with the use of low energy electron-emitting radionuclides (e.g. Tc-99m, I-123/125, Tl-201, In-111) are related to the molecular localization of the nuclides relative to DNA. It is unclear whether DNA damage caused by such nuclides in proximity to DNA is due to direct radiation effects or {sm_bullet}OH radicals. We have developed a novel method that can be used to investigate {sm_bullet}OH formation following the decay of radionuclides within specific molecular sites in chromatin. A molecular probe has been synthesized (SECCA, a derivative of coumarin) that is converted to fluorescent 7-OH-SECCA following interaction with {sm_bullet}OH in aqueous solutions. SECCA is conjugated to DNA and upon exposure to radiation produces a fluorescent signal that quantitates {sm_bullet}OH at the site to which it is conjugated. The fluorescent product 7-OH-SECCA can be generated only by {sm_bullet}OH and not by direct radiation action. SECCA-DNA conjugates were irradiated by I-125 or Tc-99m. These nuclides were associated with DNA via modified polylysine probes, and the induction of fluorescence indicating {sm_bullet}OH formation was recorded. Addition of the {sm_bullet}OH scavenger DMSO failed to modify the fluorescent signal, indicating the proximity of {sm_bullet}OH formation to DNA and the inability of scavengers to modify damage by low energy electron emissions. This is not the case with gamma irradiation. The present molecular dosimeter approach allows real-time optical registration of {sm_bullet}OH formation and application of chromatin damage assays on the same sample.
- OSTI ID:
- 197955
- Report Number(s):
- CONF-940605-; ISSN 0161-5505; TRN: 95:007029-0095
- Journal Information:
- Journal of Nuclear Medicine, Vol. 35, Issue Suppl.5; Conference: 41. annual meeting of the Society of Nuclear Medicine, Orlando, FL (United States), 5-8 Jun 1994; Other Information: PBD: May 1994
- Country of Publication:
- United States
- Language:
- English
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