U556428.pdf (14.58 MB)
DNA strand breaks induced by gamma-ray irradiation.
thesisposted on 2015-11-19, 08:44 authored by Saijun. Fan
Part I: Plasmid DNA System The effects of a range of buffers and additives on the radiation damage in frozen aqueous plasmid DNA have been studied. In studies of various buffers, the results show that phosphate buffer system sensitise radiation DNA damage, EDTA and Tris present protections against DNA damage, in comparison with pure water system. In studies of other additives, radioprotection by NaI and LiCl increase with increasing concentrations, whilst radiosensitivity of DNA with Na2SO4 and NaClO4 increase with increasing their concentrations. DMSO shows a radioprotection. A range concentrations of spermidine and spermine are used to probe the radioprotection of DNA by polyamines. The results suggest that the protection efficiencies of polyamines increase with increasing their concentrations, moreover, spermine has a greater effect than spermidine. Part II: Cell system 10 mM concentration of spermine shows a radioprotection against DNA DSB and cell death. Metronidazole acts as a sensitiser in the induction of DSB and cell killing. However, spermine-linked metronidazole (AM1229) acts as radioprotectors against DSB under the condition of free-oxygen, and as sensitiser in induction of cell killing under the condition of atmospheric oxygen. The yields of DSBs are compared between cells irradiated at 77K and 0 C. The results show that there is a reduction of DSB in cells exposed at 77K, approximately 35% less than that in cells exposed at 0 C. It may suggest that ca. 65% DNA DSBs formed from direct effect, 35% from indirect effects. There is a difference of DSB yield in cells exposed to gamma-rays in the presence of hypotonic (0.05M) and hypertonic (1.5M) NaCl solutions. The results show that there is 20% increase in hypotonic solution, 8% reduction in hypertonic solution. However, these influences disappear when the cells are irradiated at 77K. The results suggest that the water concentration within cells has an effect on the radiation damage to DNA. There is no evidence to show that an adaptive response of DNA DSB is induced in cell pre-exposed to low doses and subsequently to high doses. The results might suggest that there is no a simple link between repair of DNA DSB and the induction of adaptive response which is found in chromosomal aberration.
Date of award1992-01-01
Awarding institutionUniversity of Leicester