Investigation of the oxygen effects on the side population cells derived from prostate cancer cells using a cell-killing model considering heterogeneous radiosensitivity

Saga, Ryo*; Iwamori, Kenta*; Matsuya, Yusuke  

A cell-killing model that considers radioresistant cancer stem cells (CSCs) allows for a more accurate estimation of biological effects, including survival and tumor control probability. However, the impacts of oxygen conditions on the radiosensitivity of CSCs remain unclear. In this study, we conducted in vitro experiments and analyzed the relationship between the CSC fraction and oxygen enhancement ratio (OER) using a cell-killing model, specifically the integrated microdosimetric-kinetic (IMK) model. We utilized a cell sorter (BD FACS Aria) to sort side population (SP) cells, representing CSCs from the prostate cancer cell population, based on their Hoechst33342 efflux capacity and DNA content. We measured DNA double-strand breaks (DSBs) and cell survival of SP cells under both oxic and hypoxic conditions. The experimental results indicated reduced DSBs and increased survival in SP cells compared to the other main population cells. The model estimate showed that the OER values for MP and SP cells were 1.42 and 1.30, respectively. These results suggest that SP cells, which are rich in CSCs, display reduced oxygen effects due to their intrinsic radioresistance.