Abstract
IntroductionRadioprotective 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.MethodsT98G glioma cells were treated with 15 μM methylproamine and exposed to 137Cs γ-ray/X-ray irradiation and He2+ microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay.ResultsRadioprotection of directly targeted T98G cells by methylproamine was observed for 137Cs γ-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 conclusionMethylproamine protected targeted cells from DNA damage caused by γ-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.
Highlights
Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure
Radioprotection of directly targeted T98G cells by methylproamine was observed for 137Cs γ-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
Summary
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. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Pulse radiolysis experiments support a mechanism involving repair of transient radiation-induced oxidative lesions on DNA, by a process of electron/hole transfer from/to nearby DNAbound drug. This hypothesis is consistent with the results of recent investigations of double-stranded break induction, just an hour after irradiation, as reflected by the appearance of γH2AX foci, which serve as a sensitive marker for DNA double strand breaks [10]. The radioprotection by methylproamine, demonstrated for the clonogenic survival endpoint, can be ascribed to a decrease in the yield of early DNA damage as measured by the foci assay
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