Radiobiological Effects of the Combined Action of 1-β-D-Arabinofuranosylcytosine and Proton Radiation on B16 Melanoma in vivo

Abstract Taking into account the previously obtained data on the ability of 1-β-D-arabinofuranosylcytosine (AraC) to significantly increase the number of DNA double-strand breaks after cell culture exposure to ionizing radiation in vitro, the aim of this study was to evaluate the combined action of this compound and proton radiation at a focal dose of 10 Gy on of B16 melanoma growth and a number of processes associated with the radiation response of the tumor—in comparison with those after single irradiation with a proton beam in vivo. Significant tumor growth inhibition was established in both groups of irradiated animals in comparison with the control; the most pronounced effect was observed with combined exposure. Molecular cell parameters of cell death and proliferative activity changed approximately to the same extent after the studied exposures compared with the control. However, the proportion of cancer stem cells was reduced by 3.1 times after combined exposure compared with single irradiation (p = 0.003), which, at least in part, explains the greatest inhibition of tumor growth after irradiation in the presence of AraC.