Substructure in the Radiation Survival Response at Low Dose: Asynchronous and Partially Synchronized V79-WNRE Cells

Abstract

The radiation survival response of asynchronously-dividing populations of the cell line V79-WNRE indicates substructure in the low dose region that can be better characterized by separately fitting the data within the low and high dose regions to the linear—quadratic (LQ) equation. Flow cytometry and cell sorting techniques have been used to determine the response of both asynchronous populations and synchronous populations obtained by mitotic selection with or without an additional drug block. The statistically significant substructure which is present in the radiation response of asynchronous cells is absent in G₁/S cells synchronized by mitotic selection followed by hydroxyurea (or aphidicolin) accumulation at the G₁/S boundary. Such G₁/S populations have a radiation response that is well characterized by a single LQ expression over 3 logs of cell inactivation. In contrast, the radiation response of cells synchronized by mitotic selection alone and irradiated in early G₁ shows substantial substructure when fitted to the LQ equation, reflecting some radioresistance at high dose. While this response is well described by a single hit plus multitarget equation, it is possible that the small proportion (< 5%) of interphase cells in such mitotically-selected populations may be responsible for the resistance observed at higher doses.