1989). for Auger electron emitters. These studies highlight the part of DNA topology in DSB production by Auger emitters and underscore the failure of current theoretical dosimetric methodsper seto forecast the magnitude of DSB. Keywords:DNA strand break, DNA topology, Auger electron,123I,125I == Intro == Many radionuclides show the Auger effect, a trend which is characterized by the emission of a cascade of low-energy electrons (Auger 1925). The decay of such radioactive atoms is definitely accompanied from the creation of a main vacancy in the inner shell consequent to electron capture and/or internal conversion and prospects to the emission of X-ray photons and monoenergetic Auger or Coster-Kronig electrons with energies ranging from a few eV to ~1 keV (Cole 1969,Pomplun et al. 1987,Kassis 2004). Auger electrons travel a short range of 2 to 500 nm; consequently, they behave Rabbit Polyclonal to SIRPB1 like high linear energy transfer (LET) radiation (~2 to ~25 keV/m) and must be in close proximity to DNA, to cause cytotoxicity (Sastry and Rao 1984,Charlton et al. 1987,Kassis 2004). Among the Auger electron emitters, Iodine-125 and iodine-123 have attracted Befetupitant considerable attention in the development of malignancy therapy (Bloomer and Adelstein 1977,Kassis et al. 1998,Kassis 2004,Kassis et al. 2004). The related size of an iodine atom and a CH3group offers permitted thein vivoincorporation of radioiodine as 5-[125I/123I]iodo-2-deoxyuridine (125IUdR,123IUdR) in the place of thymidine into the nuclear DNA during cell division, therefore facilitating the proximity of the decaying radioactive iodine atom to the DNA strand and inducing cell destroy (Hofer and Hughes 1971,Feinendegen 1975,Chan et al. 1976,1977,Makrigiorgos et al. 1989). Iodine-125-labeled DNA intercalators (Martin 1977,Kassis et al. 1989),125I-labeled benzimidazole minor-groove binders such Hoechst 33342 and 33258 (Martin and Holmes 1983,Kassis et al. 1999a,1999b,2000),123I-labeled steroid hormones (DeSombre et al. 1992,DeSombre et al. 2000),125I-internalizing antibodies and125I-deoxycytidine in homopyrimidine triplex-forming oligonucleotides (Panyutin et al. 2000,2001) have also been used in positioning radioiodine decay proximal to the DNA in the nucleus. Historically, radioiodine has been useful in the analysis and treatment of thyroid-related diseases (Rawson et al. 1951). Recently,123I, which emits a 159 keV-photon, offers emerged as an alternative for thyroid imaging by solitary photon emission computed tomography (SPECT) (Reynolds and Robbins 1997,Yaakob et al. 1999). Unlike131I, the decay of123I does not emit-particles and, consequently, delivers less radiation to the surrounding normal tissue. However, when123I is definitely proximal to nuclear DNA, the cytotoxicity of Auger electron cascade could be a nuisance in123I imaging. Hence, a clear understanding of the mechanisms underlying123I induced DNA damage and cell death is necessary in developing reliable radiation safety tools to protect normal cells from radiation risk during these diagnostic methods. We have been interested in exploring the biophysical mechanisms underlying DNA damage induced by Auger emitters, particularly125I and123I. We had hypothesized that DNA compaction favors the formation of >1 DSB byOH-mediated indirect mechanisms when DNA-incorporated125I decays (Walicka et al. 1998). As a result, a higher DSB was expected Befetupitant for the supercoiled (SC) form of naked plasmid DNA due to its compacted state than for its torsionally relaxed, non-supercoiled counterpart, the linear (L) form. However, our recent study (Balagurumoorthy et al. 2008) using the minor-groove binder125I-labeledm-iodo-p-ethoxyHoechst 33342 (125IEH) showed that supercoiling of naked plasmid DNA significantly reduces the magnitude of125I-induced DSB yield and affects the mechanism (direct versus indirect) of DSB production. A 3-collapse higher DSB yield is observed for torisonally relaxed L DNA (~1.6 per decay of125I) than for SC DNA (~0.5 per125I decay), and both direct and indirect mechanisms produce DSB in the L form compared Befetupitant with only the direct mechanism in the SC form. In here, we compared123IEH-induced DSB yields for SC and L forms of pUC19 plasmid.