Radioprotection of targeted and bystander cells by methylproamine

Introduction Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. Methods T98G glioma cells were treated with 15 mu M methylproamine and exposed to Cs-137 gamma-ray/X-ray irradiation and He2+ microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or gamma H2AX assay. Results Radioprotection of directly targeted T98G cells by methylproamine was observed for Cs-137 gamma-rays and X-rays but not for He2+ charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He2+ ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Discussion and conclusion Methylproamine protected targeted cells from DNA damage caused by gamma-ray or X-ray radiation but not He2+ ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received.