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

University of British Columbia

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.

Text

2010-10-05

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http://hdl.handle.net/2429/28950

Physics

University of British Columbia

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