title: Dose response of soft X-ray-induced bystander cell killing affected by p53 status.
abstract: A radiation-induced bystander response, which is generally defined as a cellular response that is induced in nonirradiated cells that received bystander signals from directly irradiated cells within an irradiated cell population. In our earlier X-ray microbeam studies, bystander cell killing in normal human fibroblasts had a parabolic relationship to the irradiation dose. To elucidate the role of p53 in the bystander cell killing, the effects were assessed using human non-small cell lung cancer cells expressing wild-type or temperature-sensitive mutated p53. The surviving fraction of bystander wild-type p53 cells showed a parabolic relationship to the irradiation dose; survival was steeply reduced up to 0.45 Gy, recovered toward to 2 Gy, and remained at control levels up to 5 Gy. In contrast, in the mutated p53 cells at a nonpermissive temperature, the surviving fraction was steeply reduced up to 1 Gy and remained at the reduced level up to 5 Gy. When the mutated p53 cells were incubated at a permissive temperature, the decrease in the surviving fraction at 2 Gy was suppressed. The wild-type p53 cells were not only restrained in releasing bystander signals at 2 Gy, but were also resistant to the signals released by the mutated p53 cells. These results suggest that the X-ray-induced bystander cell killing depends on both the irradiation dose and the p53 status of the targeted cells and the bystander cells.
authors.affiliation: Radiation Safety Research Center, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae, Tokyo 201-8511, Japan. mstomita@criepi.denken.or.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Tomita
authors.forename: Munetoshi
authors.initials: M
authors.lastname: Maeda
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D024201:Bystander Effect / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003470:Culture Media / Q000737:chemistry; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology; D020218:Response Elements / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013696:Temperature; D015533:Transcriptional Activation / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D003470:Culture Media; D052246:Cyclooxygenase 2 Inhibitors; D016166:Free Radical Scavengers; D009573:Nitrites; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D004247:DNA