title: Neutron exposures in human cells: bystander effect and relative biological effectiveness.
abstract: Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001). These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0 ± 0.13 for micronuclei and 5.8 ± 2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Isheeta
authors.initials: I
authors.lastname: Seth
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Schwartz
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stewart
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Emery
authors.affiliation: Department of Radiation Oncology, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Joiner
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: James D
authors.initials: JD
authors.lastname: Tucker
mesh_terms: D024201:Bystander Effect / Q000528:radiation effects*; D002460:Cell Line; D048750:Cell Nucleus Division / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D004249:DNA Damage; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects; D015162:Micronucleus Tests / Q000379:methods; D009502:Neutrons; D017785:Photons; D012062:Relative Biological Effectiveness
chemical_list: D003037:Cobalt Radioisotopes