MARC 主機 00000nam  2200373   4500 
001    AAI3185033 
005    20061222092047.5 
008    061222s2005                        eng d 
020    9780542263477 
035    (UnM)AAI3185033 
040    UnM|cUnM 
100 1  Purkayastha, Shubhadeep 
245 10 Physico-chemical mechanisms of direct effect damage in DNA
       exposed to ionizing radiation 
300    279 p 
500    Source: Dissertation Abstracts International, Volume: 66-
       08, Section: B, page: 4121 
500    Supervisor:  William A. Bernhard 
502    Thesis (Ph.D.)--University of Rochester, 2005 
520    Direct-type damage is the composite of the damage arising 
       from direct ionization of DNA or from the transfer of dry 
       electrons and holes to the DNA from its surrounding 
       hydration waters. Here we test the hypothesis that the 
       majority of DNA strand breaks produced by direct-type 
       effects are due to sugar free radical precursors. The free
       radical dose response for crystalline DNA samples 
       irradiated at 4 K was determined using electron 
       paramagnetic resonance (EPR) spectroscopy. It was found 
       that the dose response for sugar radicals correlates well 
       with that of strand break products, supporting the 
520    In X-irradiated plasmid DNA, free radical yields were 
       measured by EPR at 4 K, and single strand breaks (ssb) and
       double strand breaks (dsb) were measured by gel 
       electrophoresis. We determined the yields of (i) total DNA
       radicals, G(Sigmafr), (ii) sugar trapped radicals, Gsugar 
       (fr), (iii) prompt single strand breaks, Gprompt(ssb), 
       (iv) total single strand breaks, Gtotal(ssb), and (v) 
       double strand breaks, G(dsb). The most provocative finding
       is that the yield of total single strand breaks exceeds 
       the yield of trapped sugar radicals, i.e. G total(ssb) > 
       Gsugar(fr). A significant fraction of strand breaks, 
       therefore, is derived from precursors other than trapped 
       DNA radicals. A novel mechanism is proposed whereby strand
       breaks are produced by two one-electron oxidations at a 
       single site; the first oxidation is by direct ionization 
       and the second is by a mobile guanine radical cation 
520    The role of DNA hydration (Gamma) in the induction of 
       strand breaks and base lesions in pUC18 plasmid was 
       investigated. The G(Sigmafr) and G total(ssb), are found 
       to increase in tandem from Gamma = 2.5 to Gamma = 22.5 
       waters/nucleotide. The ratio Gtotal(ssb)/Gsugar(fr) 
       however, is seen to decrease with increasing hydration. 
       These findings argue in favor of the double oxidation at 
       one site mechanism. The yield of specific types of base 
       lesions was measured using base-excision repair 
       endonucleases, Fpg and Nth. Base damage and strand break 
       yields were found to be comparable. A working model that 
       explains end product formation by direct effects in DNA is
590    School code: 0188 
590    DDC 
650  4 Biophysics, General 
650  4 Chemistry, Radiation 
650  4 Biology, Molecular 
690    0786 
690    0754 
690    0307 
710 20 University of Rochester 
773 0  |tDissertation Abstracts International|g66-08B 
856 40 |u