title: X-ray-induced bystander responses reduce spontaneous mutations in V79 cells.
abstract: The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm(2) 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10(-)(5) (background level), and the frequency decreased to 5.3 × 10(-)(6) with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations.
authors: Proton Medical Research Group, Research and Development Department, The Wakasa Wan Energy Research Center, 64-52-1 Nagatani, Tsuruga-shi, Fukui 914-0192, Japan.
authors: Munetoshi
authors: M
authors: Maeda
authors: Katsumi
authors: K
authors: Kobayashi
authors: Hideki
authors: H
authors: Matsumoto
authors: Noriko
authors: N
authors: Usami
authors: Masanori
authors: M
authors: Tomita
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D024201:Bystander Effect / Q000502:physiology* / Q000528:radiation effects*; D002460:Cell Line; D002869:Chromosome Aberrations / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects; D009154:Mutation / Q000235:genetics* / Q000528:radiation effects; D009569:Nitric Oxide / Q000378:metabolism*; D011829:Radiation Dosage
chemical_list: D009569:Nitric Oxide
keywords: cell death; microbeam irradiation; mutation; nitric oxide; radiation-induced bystander responses
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