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dc.contributor.advisorSanche, Léon
dc.contributor.advisorWagner, Richard J.
dc.contributor.authorKhorsandgolchin, Ghazalfr
dc.date.accessioned2019-08-05T13:50:36Z
dc.date.available2019-08-05T13:50:36Z
dc.date.created2019fr
dc.date.issued2019-08-05
dc.identifier.urihttp://hdl.handle.net/11143/15813
dc.description.abstractNumerous experimental studies have shown that 5-15 eV electrons induce strand breaks in DNA, at energies below the ionization threshold of DNA components. In this energy range, DNA damage arises principally by the formation of transient negative ions (TNIs), decaying into the dissociative electron attachment (DEA), and electronic excitation of dissociative states. Here, we analyse by LC-MS/MS the degradation products from bombarment of the DNA component TpT, with electrons of ∼1.8 eV that can only produce damage by DEA. Three major types of damage were observed: 1) fragmentation involving C-O bond cleavage; 2) release of non-modified thymine; and 3) reduction of thymine to 5,6-dihydrothymine. C-O bond cleavage at C3’ gave thymidine 5’-monophosphate (TMP5’) and 2’,3’-dideoxythymidine (ddT3’) in a 2-fold greater yield than cleavage at the 5’ position, which gave thymidine 3’-monophosphate (TMP3’) and 2’,5’-dideoxythymidine (ddT5’). Interestingly, the yield of thymidine monophosphates was higher than that of the corresponding dideoxythymidine product, suggesting that other reactions contributed to phosphodiester bond cleavage. The formation of ddT3’ and ddT5’ was lowered upon irradiation of either TMP5’ or TMP3’ and it decreases further by several fold in the case of thymidine, underlining the critical role of the phosphate group in C-O bond cleavage. The release of non-modified thymine cannot be explained by C-N glycosidic bond cleavage, because of the lack of mass balance between the release of non-modified thymine and abasic sugar fragments. Thus, very low energy electrons (vLEEs) do not efficiently break the C-N bond by DEA. Lastly, vLEE irradiation of TpT converted thymine to 5,6-dihydrothymine, indicating attachment of the electron to the 5,6-double bond of thymine to produce the thymine anion radical. In summary, this work demonstrates that vLEEs induce C-O bond cleavage of the phosphodiester bond as a major reaction pathway.fr
dc.language.isoengfr
dc.publisherUniversité de Sherbrookefr
dc.rights© Ghazal Khorsandgolchinfr
dc.rightsAttribution - Pas d’Utilisation Commerciale - Partage dans les Mêmes Conditions 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/2.5/ca/*
dc.subjectIonizing radiationfr
dc.subjectDNA damagefr
dc.subjectMass spectrometryfr
dc.subjectSecondary electronsfr
dc.titleDNA damage in TpT induced by very low energy electronsfr
dc.typeMémoirefr
tme.degree.disciplineSciences des radiations et imagerie biomédicalefr
tme.degree.grantorFaculté de médecine et des sciences de la santéfr
tme.degree.levelMaîtrisefr
tme.degree.nameM. Sc.fr


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© Ghazal Khorsandgolchin
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