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Prediction Of Radiosensitivity Of Cells By Heavy Ions Induced Chromosome Breaks

Posted on:2013-07-17Degree:MasterType:Thesis
Country:ChinaCandidate:Q WangFull Text:PDF
GTID:2234330392950837Subject:Cell biology
Abstract/Summary:PDF Full Text Request
Radiotherapy is one of the most effective methods for the treatment of malignant tumors.In comparisons with treatments involving X-rays and c-rays, the high rate of cure with heavyions is due to physical characteristics, such as high linear energy transfer (LET) at the Braggpeak region, low side-scattering, etc. As reported in previous studies, cells exposed to variousradiations resulted in chromosome breaks including chromatid discontinuity, misalignment ofthe distal, chromatid ring and so on. These potential changes possibly cause the death of cells.Most of the above studies have applied the premature chromosome condensed technique; thistechnique can be operated both by cell fusion and drug induced, but the former is lowefficiency. The chemically induced premature condensed chromosome technique, an easy andquick method on detecting chromosome breakage was widely applied in the radiobiologicaland oncology works. Murakami used atom force microscope (AFM) and studied the accuracyof chemically induced PCC breakages in comparison with the results acquired through lightmicroscope vision. There was no significant difference between the two methods, and thisvalidated that the PCC technique was suitable and reliable for radiation induced chromosomedamage analysis. Through former researches, employed different heavy ions with variousLET and X-rays to investigate the radiation induced chromosome breaks both in humannormal fibroblast cells and malignant cells. The number of chromatid breaks was found to belinearly correlated with the absorbed dose of radiation. In comparisons with experimentsinvolving X-rays or γ-rays, more isochromatid breaks were produced by exposure to heavyions, while chromatid-type breaks were dominant when cells exposed to X/gamma rays.Meanwhile, some scientists addressed the correlation between intrinsic radiosensitivity andunrejoined PCC breaks. This may be another way to study the intrinsic radiosensitivity andhow it correlates with the other radiations. Before clinical treatment can begin, the therapeuticregimen must be defined and during this stage information on individual patientradiosensitivity would be of great medical value. Several methods have been developed tomeasure cell radiosensitivity, for example, the colony assay and the cytoplasm-blockedmicronuclei assay. Previous data have shown that these two methods are not ideal. Briefly,the colony assay is the classic method for detecting radiosensitivity. The assay is precise butthe formation of a clone takes at least7days. Conflicting views have been held concerning the detection of cell radiosensitivity with the cytoplasm blocked micronuclei method. Somescientists consider that there is a good relationship between the radiation-induced micronucleiand cell radiosensitivity, but others do not agree. Yang further improved the PCC technique inthe area of chromosome analysis, that is, we have found radiation inducedchromatid/isochromatid breaks were closely correlated with cell survival when exposed toheavy charged carbon ions. These results suggested chemically induced PCC breaks can bepossibly regarded as a good signal to predict radiosensitivity when exposed to high LETradiations. However, we do not think it is perfectly ideal to predict radiosensitivity by usingexperimental PCC technique, heavy ions are of great capability in killing cells, and onlinedetection would bring vast irradiation risk to operators. Thus the main idea of the presentstudy is to simulate the chromosome breaks and validate the simulation combined withexperimental PCC technique.The main results were as follows: This suggested that higher relative biologicaleffectiveness of heavy ions was closely correlated with its physical characteristics, also, a safeapproach on predicting chromosome breaks in cells exposed to heavy ions at off-lineenvironment come to be considered. Furthermore, three key factors influencing the theoreticalsimulation was investigated and discussed.
Keywords/Search Tags:heavy ions, radiosensitivity, chromosome break, theoretical simulation
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