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Presence of cell-cycle dependent substructure at low dose in the radiation survival response of asynchronous V79-WNRE cells

Survival studies using cell sorting techniques together with data averaging on asynchronously dividing V79-WNRE cells reveal statistically significant evidence of substructure in the radiation survival response at low dose (2 to 3 Gy) that cannot be adequately characterized by a single linear-quadratic function, S = exp( -αD -βD²). The data suggest a two-component response that is particularly evident when plotted in the linear form of the linear-quadratic equation, -ln(S)/D = α + βD. Application of other survival models (Single Hit + Multi Target and Repair-Misrepair) does not eliminate the substructure.
The substructure may result from subpopulations of cells at different stages of the cell cycle, which differ in their radiosensitivity, giving rise to a two-component survival response. In order to explore this hypothesis, studies were carried out with populations of partially synchronized cells. The mitotic selection technique was employed alone or in combination with 12 hours exposure to 1 mM hydroxyurea or 1 μg/ml aphidicolin to obtain large numbers of synchronized cells. G1/S phase populations obtained by mitotic selection followed by hydroxyurea or aphidicolin do not show the substructure found for asynchronous cells, thus supporting the hypothesis. G1 phase populations obtained by mitotic selection alone revealed substructure which could be characterized by a single fit to the RMR or SH+MT models. Structure was also present in the response of heterogeneous S/G2 phase populations synchronized by mitotic selection followed by hydroxyurea, but may not be present in the response of S phase populations synchronized by mitotic selection alone. The data are consistent with the hypothesis that the substructure is a result of sensitive (G1, G2 or M) and resistant (S) subpopulations of cells. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

Identiferoai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/28950
Date January 1990
CreatorsSkwarchuk, Mark William
PublisherUniversity of British Columbia
Source SetsUniversity of British Columbia
LanguageEnglish
Detected LanguageEnglish
TypeText, Thesis/Dissertation
RightsFor non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

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