PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 16808607

A dose threshold for a medium transfer bystander effect for a human skin cell line.

Zhengfeng Liu·Carmel E Mothersill·Fiona E McNeill·Fiona M Lyng·Soo Hyun Byun·Colin B Seymour·William V Prestwich
View original source ↗Export metadata ↓

Abstract

The existence of radiation-induced bystander effects mediated by diffusible factors is now accepted, but the mechanisms and precise behavior at low doses remain unclear. We exposed cells to gamma-ray doses in the range 0.04 mGy-5 Gy, harvested the culture medium, and transferred it to unirradiated reporter cells. Calcium fluxes and clonogenic survival were measured in the recipients. We show evidence for a dose threshold around 2 mGy for the human skin cell line used with a suggestion of increased survival below that dose. Similar experiments using direct gamma irradiation showed no reduction in survival until the dose exceeded 7 mGy. Preliminary data for neutrons where the gamma-ray dose was kept below the bystander threshold do not show a significant bystander effect in the dose range 1-33 mGy. A lack of a bystander response with neutrons occurred at around 1 Gy, where significant cell killing from direct irradiation was observed. The result may have implications for understanding the role of bystander effects at low doses.

Explore related subjects

Bystander EffectCell LineCell SurvivalCulture MediaDifferential ThresholdDose-Response Relationship, RadiationHumansRadiation DosageSkinSkin Physiological PhenomenaJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zhengfeng Liu, Carmel E Mothersill, Fiona E McNeill, Fiona M Lyng, Soo Hyun Byun, Colin B Seymour, William V Prestwich. 2006. A dose threshold for a medium transfer bystander effect for a human skin cell line.. https://doi.org/10.1667/rr3580.1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Radiation-induced bystander effect: activation of signaling molecules in K562 erythroleukemia cells.

Gap junction independent signaling mechanism was investigated using K562 human erythroleukemia cells. They were exposed to 2, 5, or 10 Gy of (60)Co gamma irradiation, the medium isolated 20 min post-irradiation and added to fresh cells. Evidence of radiation-induced bystander effect was observed wherein there was activation of p21, nuclear factor-kappaB (NF-kappaB), Bax, Bcl-2 and cleavage of poly(ADP-ribose) polymerase in bystander cells. The study implicates the involvement of signaling molecules released into the medium and factors like stable free radicals that are generated in the surrounding medium. The response elicited appears to be primarily via NF-kappaB and p21 activation.

Bystander Effect↗
PubMed2007

Induction of inducible NO synthase in bystander human T cells increases allogeneic responses in the vasculature.

Inducible NO synthase (iNOS) in human T cells is implicated in the pathogenesis of graft arteriosclerosis. Here we analyze the regulation and role of iNOS in human peripheral blood T cells. Allogeneic endothelial cells (EC) or dermal fibroblasts induce iNOS mRNA and protein expression, as well as enzymatic activity in primary human CD8 T cells. Although human EC activate T cells through the presentation of alloantigen, iNOS induction is confined to nonactivated T cells and does not depend on MHC molecules or costimulators. iNOS induction does involve new transcription and depends on NF-kappaB. JAK signaling, initiated during T cell activation, inhibits iNOS expression. Even though iNOS is confined to bystander T cells, inhibition of iNOS activity reduces T cell proliferation in response to allogeneic EC, and addition of low levels of a NO donor rescues T cell responses. Similarly, iNOS is preferentially expressed by nonproliferating T cells within allografted arteries in vivo, and inhibition of iNOS activity reduces the number of activated T cells in these artery segments. These data identify a previously undescribed mechanism for enhanced activation of alloreactive T cells, namely stromal cell-mediated induction of iNOS in bystander T cells.

Bystander Effect↗
PubMed2007

The mechanism underlying defective Fcgamma receptor-mediated phagocytosis by HIV-1-infected human monocyte-derived macrophages.

Clearance of IgG-opsonized erythrocytes is impaired in HIV-1-infected patients, suggesting defective FcgammaR-mediated phagocytosis in vivo. We have previously shown defective FcgammaR-mediated phagocytosis in HIV-1-infected human monocyte-derived macrophages (MDM), establishing an in vitro model for defective tissue macrophages. Inhibition was associated with decreased protein expression of FcR gamma-chain, which transduces immune receptor signals via ITAM motifs. FcgammaRI and FcgammaRIIIa signal via gamma-chain, whereas FcgammaRIIa does not. In this study, we showed that HIV-1 infection inhibited FcgammaRI-, but not FcgammaRIIa-dependent Syk activation in MDM, showing that inhibition was specific for gamma-chain-dependent signaling. HIV-1 infection did not impair gamma-chain mRNA levels measured by real-time PCR, suggesting a posttranscriptional mechanism of gamma-chain depletion. HIV-1 infection did not affect gamma-chain degradation (n = 7, p = 0.94) measured in metabolic labeling/chase experiments, whereas gamma-chain biosynthesis was inhibited (n = 12, p = 0.0068). Using an enhanced GFP-expressing HIV-1 strain, we showed that FcgammaR-mediated phagocytosis inhibition is predominantly due to a bystander effect. Experiments in which MDM were infected in the presence of the antiretroviral drug 3TC suggest that active viral replication is required for inhibition of phagocytosis in MDM. These data suggest that HIV-1 infection may affect only gamma-chain-dependent FcgammaR functions, but that this is not restricted to HIV-1-infected cells.

Bystander Effect↗