Detalhes do Documento

The role of halouracils in radiotherapy studied by electron transfer in atom-molecule collisions experiments

Autor(es): Antunes, Rodrigo Augusto Ferreira

Data: 2011

Identificador Persistente: http://hdl.handle.net/10362/6653

Origem: Repositório Institucional da UNL

Assunto(s): Radiosensitizers; Electron transfer; Negative ion formation; Atom-molecule collisions; Time-of- flight mass spectrometer


Descrição

The role of ionising radiation as a source of damage to living tissues and cells has been recognized as a key issue regarding cellular DNA integrity and, ultimately, mutagenesis. The lethal effect of radiation, despite being most of the time undesired, can sometimes be useful, as is the case of radiation therapy. However, still the major concern in medicine is that only the cancerous cell material should be destroyed, keeping as much as possible healthy tissue unaffected. One way to control this damage seems to be the application of radiosensitizers that are incorporated into cancer cells. The cancer tissue doped with these radiation sensitizing molecules may be destroyed preferentially under radiation exposure, in very well defined places and even with radiation doses which may be low enough to prevent healthy cell material to be affected in the surrounding medium. This leads to nanodosimetry and so the sorts of interactions have now to be described at the molecular level. Upon irradiation, the most abundant secondary species produced along the radiation track are low energy electrons and so the study of electron induced damage to biological relevant molecules seems indubitably relevant. The research described in this thesis covers for the first time the study of electron transfer on two halouracils (5-chlorouracil and 5-fluorouracil) and isolated DNA/RNA basis (thymine and uracil)by atom-molecule collisions. In order to investigate such molecules, a crossed beam experiment, comprising a neutral potassium beam and a biolomecular effusive beam, was improved and a time-offlight mass spectrometer implemented allowing for the detection of negative ion formation following electron transfer processes in atom-molecule collisions. In these experiments the anionic fragmentation patterns and formation yields were obtained. These results are shown to be significantly different from the dissociative electron attachment (free electrons) results, unveiling that the damaging potential of secondary electrons to biomolecules can be somewhat underestimated. In addition, the halouracils sensibility to electron induced damage appears to be enhanced with respect to thymine and uracil, which may be extremely relevant as it reinforces their effectiveness as radiosensitizer molecules.

Dissertação para obtenção do Grau de Doutor em Engenharia Física

Tipo de Documento Tese de doutoramento
Idioma Inglês
Orientador(es) Loureiro, Paulo
Contribuidor(es) Antunes, Rodrigo Augusto Ferreira
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