Bystander response in human lymphoblastoid TK6 cells

Grifalconi, Mauro; Celotti, Lucia; Mognato, Maddalena

doi:10.1016/j.mrfmmm.2007.06.004

Cited by 18 publications

(8 citation statements)

References 46 publications

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“…Apoptosis induction was measured also by the caspase-3 activation using the ApoAlert® Caspase Fluorescent Assay kit according to manufacturer’s instructions and as previously described [36]. Cell lysates (1 × 10 6 cells) were prepared at the end of 2 h treatment in serum-free medium followed by a recovery of 22 h in complete medium and analyzed with a Perkin-Elmer LS-50 B spectrofluorimeter.…”

Section: Methodsmentioning

confidence: 99%

The toxicity outcome of silica nanoparticles (Ludox®) is influenced by testing techniques and treatment modalities

et al. 2012

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We analyzed the influence of the kind of cytotoxicity test and its application modality in defining the level of hazard of the in vitro exposures to nanostructures. We assessed the cytotoxicity induced by two different Ludox® silica nanoparticles (NPs), AS30 and SM30, on three human cell lines, CCD-34Lu, A549, and HT-1080. Dynamic light scattering measurements showed particle agglomeration when NPs are diluted in culture medium supplemented with fetal calf serum. We examined the impact of such particle aggregation on the cytotoxicity by exposing the cells to NPs under different treatment modalities: short incubation (2 h) in serum-free medium or long incubation (24–72 h) in serum-containing medium. Under this last modality, NP suspensions tended to form aggregates and were toxic at concentrations five- to tenfold higher than in serum-free medium. The results of cell survival varied considerably when the long-term clonogenic assay was performed to validate the data of the short-term MTS assay. Indeed, the half maximum effective concentrations (EC50) in all the three cell lines were four- to fivefold lower when calculated from the data of clonogenic assay than of MTS. Moreover, the mechanisms of NP toxicity were cell-type-specific, showing that CCD-34Lu are prone to the induction of plasma membrane damages and HT-1080 are prone to DNA double-strand break and apoptosis induction. Taken together, our results demonstrate that the choice of testing strategy and treatment conditions plays an important role in assessing the in vitro toxicity of NPs.Figure Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-012-6246-6) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

The toxicity outcome of silica nanoparticles (Ludox®) is influenced by testing techniques and treatment modalities

et al. 2012

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“…Awareness of radiation-induced bystander effects has led to a paradigm shift in radiobiology. While the ability of ionizing radiation to induce the secretion of media soluble factors has been documented, 14,15 there is very little literature on the ability of other DNA damaging agents to do the same. However, as we have shown in this review, chemicals are also capable of inducing bystander effects through media-secreted factors.…”

Section: Combined Radio-chemotherapymentioning

confidence: 99%

Bystander effects and radiotherapy

Marín

Martín

Liñan

et al. 2015

Reports of Practical Oncology & Radiotherapy

160

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Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.

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“…Given that the multiple markers that have been used to study the BSE, that is, micronuclei formation (Yang et al, 2007), clonogenic survival (O'NeillMehlenbacher et al, 2007), apoptosis (Grifalconi et al, 2007) and sister chromatid exchange (SCE) (Nagasawa et al, 2005) (Figure 1), are themselves considered to be detrimental, it has been assumed that the BSE is harmful to neighboring cells. However, it has also been proposed that the BSE may actually be beneficial at a tissue level; cells exposed to a bystander signal are more radioresistant to subsequent IR-induced damage indicative of an adaptive response (Iyer and Lehnert, 2002).…”

Section: Introductionmentioning

confidence: 99%

DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals

et al. 2008

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The phenomenon by which irradiated cells influence nonirradiated neighboring cells, referred to as the bystander effect (BSE), is not well understood in terms of the underlying pathways involved. We sought to enlighten connections between DNA damage repair and the BSE. Utilizing sister chromatid exchange (SCE) frequencies as a marker of the BSE, we performed cell transfer strategies that enabled us to distinguish between generation versus reception of a bystander signal. We find that DNAdependent Protein Kinase catalytic subunit (DNA-PKcs) and Ataxia Telangectasia Mutated (ATM) are necessary for the generation of such a bystander signal in normal human cells following gamma (c)-ray exposure, but are not required for its reception. Importantly, we also show that directly irradiated human cells do not respond to receipt of a bystander signal, helping to explain why the BSE is a low-dose phenomenon. These studies provide the first evidence for a role of the DNA damage response proteins DNA-PKcs and ATM specifically in the generation of a bystander signal and intercellular signaling.

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Bystander response in human lymphoblastoid TK6 cells

Cited by 18 publications

References 46 publications

The toxicity outcome of silica nanoparticles (Ludox®) is influenced by testing techniques and treatment modalities

The toxicity outcome of silica nanoparticles (Ludox®) is influenced by testing techniques and treatment modalities

Bystander effects and radiotherapy

DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals

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