Enhanced cellular radiation sensitivity of androgen-independent human prostate tumor cells by onconase

The RNase-like onconase, isolated from amphibian oocytes, showed increases in median tumor pO(2) in solid tumors (1). This led us to consider if oncon ase could decrease cellular O-2 consumption (QO(2)) on 9L rat glioma as wel l as DU145 human prostate adenocarcinoma cells. Using a Clark-type electrod e chamber; we observed that onconase significantly inhibited QO(2) in both tumors we tested. Since onconase-induced reduction in QO(2) could lead to i ncreases in radiation sensitivity due to the diffusion of O-2 to previously hypoxic tumor cells, we used androgen-insensitive DU145 cells to study onc onase-induced changes in radiation sensitivity in vitro. Radiation sensitiz ation was achieved with >5 mu g/ml of onconase, regardless of the p53 statu s of tumor cells. Data presented here suggested that onconase-induced enhan cement in radiation sensitization in vitro of androgen-insensitive prostate cancel cells warranted further studies of radiation responses in vivo, pri or to clinical settings for the advanced-stages of prostate cancel.