title: Radioprotection of targeted and bystander cells by methylproamine.
abstract: BACKGROUND
  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 μM methylproamine and exposed to (137)Cs γ-ray/X-ray irradiation and He(2+) microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay.
  
  
  RESULTS
  Radioprotection of directly targeted T98G cells by methylproamine was observed for (137)Cs γ-rays and X-rays but not for He(2+) charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He(2+) 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.
  
  
  CONCLUSIONS
  Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He(2+) ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received.
authors.affiliation: Centre for Cancer Research & Cell Biology, Queen's University Belfast, Belfast, UK, s.burdakrothkamm@yahoo.co.uk.
authors.forename: Susanne
authors.initials: S
authors.lastname: Burdak-Rothkamm
authors.forename: Andrea
authors.initials: A
authors.lastname: Smith
authors.forename: Pavel
authors.initials: P
authors.lastname: Lobachevsky
authors.forename: Roger
authors.initials: R
authors.lastname: Martin
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
mesh_terms: D001562:Benzimidazoles / Q000494:pharmacology*; D024201:Bystander Effect; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D006801:Humans; D011837:Radiation-Protective Agents / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D011837:Radiation-Protective Agents; C483319:methylproamine