Loading...
Please wait, while we are loading the content...
Similar Documents
Effets des radiations gamma et des électrons de basse énergie sur la fonctionnalité de l'ADN
| Content Provider | Semantic Scholar |
|---|---|
| Author | Sahbani, Saloua |
| Copyright Year | 2014 |
| Abstract | EFFECT OF GAMMA RADIATION AND LOW ENERGY ELECTRON ON THE DNA FUNCTIONALITY By Saloua Sahbani Program of Radiation Sciences and Biomedical Imaging Thesis submitted to the Faculty of Medicine and Health Sciences for the degree of Doctorate of Philosophy (PhD) in Radiation Sciences and Biomedical Imaging, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Quebec, Canada It is generally accepted that DNA double-strand breaks (DSB) are among the most toxic lesions induced by ionizing radiation (IR). Unrepaired or misrepaired DSB can lead to genomic instability and cell death. It is known that concomitant chemoradiation therapy is one of the most preferred methods for the treatment of certain cancers especially in advanced stage. The yield of DSBs was increased when DNA was irradiated with low energy electron (LEEs). The aims of our study was to reassess the contribution of DSBs and other lesions induced by indirect and direct effect of IR in cell lethality. The effect of IR on the DNA functionality of the plasmid modified covalently with cisplatin was studied by measuring the transformation efficiency of the plasmid in E. coli. Cisplatin-DNA complexes were prepared such that there was an average of two cisplatin adducts per plasmid as measured by ICP-MS. Aqueous solutions of the samples were irradiated with 137 Cs -rays at various doses. Gel electrophoresis analysis shows that cisplatin enhances, by a factor of 2.6, the formation of DSB by -rays relative to those in unmodified DNA. Despite this increase, the yield of DSBs is very low and cannot explain the loss of functionality observed after transformation with plasmids modified with cisplatin. While locally multiple damaged sites (LMDS) revealed by repair enzymes Fpg (Formamidopyrimidine [fapy]-DNA glycosylase) and Nth (Endonuclease III) as DSB (nonDSB cluster damage), where their yield was increased by a factor of 2.1 when DNA was irradiated in the presence of cisplatin were able to explain the observed loss of DNA functionality. These results suggest that cisplatin may act not only as a chemotherapeutic agent, but also as an effective radiosensitizer by addition of other DNA lesions. For the first time, we could also evaluate the effect of low energy electrons (LEEs) on DNA functionality. Highly ordered DNA films were prepared on pyrolytic graphite by molecular self-assembly using 1,3-diaminopropane ions (Dap 2+ ) to bind together the plasmids and irradiated with LEE (10 eV). We concluded that in addition to CSBs, DSBs and base damage, LEEs induced the formation of non-DSB cluster damage and also induced the loss of DNA functionality under LEE irradiation. The yields of DSBs and of non-DSB cluster damage are too low and so one unable to explain the loss of DNA functionality. It seems that LEEs are able to induce a high complex damage that cannot be revealed by repair enzymes Fpg and Nth. The high complex damage is difficult to repair possibly because the repair of one lesion, may inhibit the repair of another. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://savoirs.usherbrooke.ca/bitstream/handle/11143/5976/Sahbani_Saloua_PhD_2014.pdf;jsessionid=D3A1A08028292BB1FA510DF97ADAEA2E?sequence=6 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
