Alpha-particle-induced increases in the radioresistance of normal human bystander cells.
Numerous investigators have reported that direct exposure of cells to a low dose of ionizing radiation can induce a condition of enhanced radioresistance, i.e. a "radioadaptive" response. In this report, we investigated the hypothesis that a radioadaptive bystander effect may be induced in unirradiated cells by a transmissible factor(s) present in the supernatants of cells exposed to a low dose of alpha particles. Normal human lung fibroblasts (HFL-1) were irradiated with 1 cGy of alpha particles and their supernatants were transferred to unirradiated HFL-1 cells as a bystander cell model. Compared to directly irradiated cells that were not treated with supernatants from HFL-1 cells exposed to low-dose radiation, such treatment resulted in increased clonogenic survival after subsequent exposure to 10 and 19 cGy of alpha particles. Increases in protein levels of AP-endonuclease, a redox and DNA base excision repair protein, were found in the bystander cells, but not in directly irradiated cells. Supernatants from alpha-particle-irradiated cells were also found to increase the clonogenicity of unirradiated cells. These results, in conjunction with our earlier findings that supernatants from cells exposed to a low dose of alpha particles contain growth-promoting activity, suggest that this new bystander effect may be related to an increase in DNA repair and cell growth/cell cycle regulation.
Iyer
Rashi
R
Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
Lehnert
Bruce E
BE
D000222:Adaptation, Physiological; D000512:Alpha Particles; D024201:Bystander Effect; D019757:Carbon-Oxygen Lyases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells / Q000187:drug effects / Q000528:radiation effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D018499:Linear Energy Transfer; D008168:Lung / Q000166:cytology; D008954:Models, Biological; D010084:Oxidation-Reduction; D011836:Radiation Tolerance / Q000528:radiation effects*
D017077:Culture Media, Conditioned; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase