title: TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice.
abstract: Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation.
authors.affiliation: Department of Physics, University of Oslo, 0316 Oslo, Norway ; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway.
authors.forename: Nina Jeppesen
authors.initials: NJ
authors.lastname: Edin
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Čestmír
authors.initials: Č
authors.lastname: Altaner
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Veronica
authors.initials: V
authors.lastname: Altanerova
authors.affiliation: Department of Physics, University of Oslo, 0316 Oslo, Norway ; Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg Ø. Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Ebbesen
keywords: TGF-β3; iNOS; low dose hyper-radiosensitivity; low dose-rate irradiation; whole-body irradiation