Cellular communication and bystander effects: a critical review for modelling low-dose radiation action

Ballarini, F.; Biaggi, M.; Ottolenghi, A.; Sapora, O.

doi:10.1016/s0027-5107(02)00010-6

Cited by 98 publications

(49 citation statements)

References 44 publications

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“…This now well accepted phenomenon, called the bystander effect, has been reported in various cell types and biological endpoints such as sister chromatid exchange (1, 2), clonogenic survival (3,4), micronucleus formation (5-10), chromatin damage (11), chromosome aberrations (12), foci formation (5), apoptosis (13) etc (for an overview see reviews (14)(15)(16)(17)(18)(19)(20)(21) and summaries (22,23)). Two major mechanisms are described in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Lack of Bystander Effects from High-LET Radiation for Early Cytogenetic End Points

2008

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1 Groesser, T., Cooper, B. and Rydberg, B. Lack of Bystander Effects From High LET Radiation ForEarly Cytogenetic Endpoints. Radiat. Res.The aim of this work was to study radiation induced bystander effects for early cytogenetic endpoints in various cell lines using the medium transfer technique after high and low LET radiation. Cells were exposed to 20MeV/amu Nitrogen ions, 968 MeV/amu Iron ions or 575 MeV/amu Iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, γ-H2AX foci formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronuclei formation using DNA repair proficient and deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X-rays. Although it was possible to occasionally detect an increase in chromatid break levels using Nitrogen ions and seeing a higher number of γ-H2AX foci formation using Nitrogen and Iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After pooling all the data, we could not verify a significant bystander effect for any these endpoints. Also, we did not detect a significant bystander effect for DSB induction or micronuclei formation in these cell lines or for clonogenic survival in SW48 cells.The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, literature data show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it seems possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, might be critical for inducing bystander effects. 2 INTRODUCTIONFor decades it has been a central dogma in radiation biology that the energy from ionizing radiation must be deposited in the cell nucleus of the affected cell or at least in the cell's cytoplasm to induce a radiation response.However, in the last years data have provided evidence that cells that are not hit directly by ionizing radiation are also influenced by damaged neighboring cells. This now well accepted phenomenon, called the bystander effect, has been reported in various cell types and biological endpoints such as sister chromatid exchange (1, 2), clonogenic survival (3, 4), micronucleus formation (5-10), chromatin damage (11), chromosome aberrations (12), foci formation (5), apoptosis (13) etc (for an overview see reviews (14-21) and summaries (22,23)). Two major mechanisms are described in the literature. First a transfer of factors through gap junctions (6) and second a medium mediated transport of the bystander factors independent of cell-cell contact (3,24). However, the factors that are involved in the transmission of the effects are still unknown. Due to the fact that the bystan...

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Section: Introductionmentioning

confidence: 99%

“…However, the factors that are involved in the transmission of the effects are still unknown. Due to the fact that the bystander effect can be detected at very low doses (see (20) for a review) this phenomenon is important for radiation risk assessment at doses below 1 Gy (overview (14,15,21)). …”

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Lack of Bystander Effects from High-LET Radiation for Early Cytogenetic End Points

2008

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“…The responses include changes in gene expression (Iyer and Lehnert, 2000;Azzam et al, 2002), induction of genetic effects such as mutations (Zhou et al, 2000;Nagasawa et al, 2003), DNA damage (Azzam et al, 2001;Little et al, 2003), cell killing (Lyng et al, 2002) and malignant transformation (Sawant et al, 2001). Bystander damage has been observed even at very low doses, down to the mGy level, and, with most end points, it does not increase significantly with dose (Ballarini et al, 2002). Since early in the 1990s, there has been increasing recognition of the importance of bystander effects, as they may have an impact on our understanding radiation-induced biological response mechanisms and developing risk estimations (Baverstock, 2000;Hall and Hei, 2003;Little, 2003;Mothersill and Seymour, 2003;Prise et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Evidence is accumulating that multiple signal transduction pathways are involved in this process, including oxidative metabolism Shao et al, 2003), gap junction-mediated intercellular communication (GJIC) (Azzam et al, 2001;Ballarini et al, 2002;Wang et al, 2004) and soluble extracellular factors (Iyer and Lehnert, 2000;Little et al, 2002). Earlier studies showed that bystander effects could be induced by treatment of unirradiated cells with medium taken from cell cultures previously exposed to irradiation Seymour, 1997, 1998;Mothersill, 1999, 2000;Lyng et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts

2005

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Although radiation-induced bystander effects have been demonstrated in a number of cell types, the studies have largely been performed using high linear energy transfer (LET) radiation, such as a-particles. The literature is contradictory on whether fibroblasts show bystander responses, especially after low LET radiation such as X-or c-rays and whether the same signal transmission pathways are involved. Herein, a novel transwell insert culture dish method is used to show that X-irradiation induces medium-mediated bystander effects in AGO1522 normal human fibroblasts. The frequency of micronuclei formation in unirradiated bystander cells increases from a background of about 6.5% to about 9-13% at all doses from 0.1 to 10 Gy to the irradiated cells. Induction of p21 Waf1 protein and foci of c-H 2 AX in bystander cells is also independent of dose to the irradiated cells above 0.1 Gy. In addition, levels of reactive oxygen species (ROS) were increased persistently in directly irradiated cells up to 60 h after irradiation and in bystander cells for 30 h. Adding Cu-Zn superoxide dismutase (SOD) and catalase to the medium decreases the formation of micronuclei and induction of p21 Waf1 and c-H 2 AX foci in bystander cells, suggesting oxidative metabolism plays a role in the signaling pathways in bystander cells. The results of clonogenic assay of bystander cells showed that survival of bystander cells decreases from 0 to 0.5 Gy, and then is independent of the dose to irradiated cells from 0.5 to 10 Gy. Unlike the response with p21 Waf1 expression, c-H 2 AX foci and micronuclei, adding SOD and catalase has no effect on the survival of bystander cells. The data suggest that irradiated cells release toxic factors other than ROS into the medium.

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“…In addition, different mutant strains in genes involved in antioxidant defense such as catalase and superoxide dismutase enzymes could be used [16,20]. It is known that through the lifespan of Drosophila the activity of Cat decreases [18,[23][24][25] however, the increased expression of the Cat gene does not extend the lifespan of flies, but rather protects against oxidative stress [26].…”

Section: Introductionmentioning

confidence: 99%

Action of protoporphyrin-IX (PP-IX) in the lifespan of <i>Drosophila melanogaster</i> deficient in endogenous antioxidants, Sod and Cat

Pimentel¹,

Vidal²,

Cruces³

et al. 2013

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Protoporphyirin-IX (PP-IX) is a precursor of the biosynthesis of the hemo group, most of the cytochromes and the chlorophylls. The PP-IX is used for medical purposes, and recently a report indicated that it exhibits a dual action since it can decrease or increase the genetic damage caused by N-nitroso-N-ethylurea (ENU) in somatic cells of Drosophila. PP-IX is known to be able to act as an anti-or pro-oxidant agent. The aim of the present research was to study the role of PP-IX on the lifespan of Drosophila melanogaster, taking into account the fact that increasing levels of ROS can accelerate the aging process. The Canton-S strain (CS) was used as well as Sod and Cat which are deficient in the endogenous enzymes, superoxide dismutase and catalase, respectively. Groups of females and males were treated separately with 5 mg/ml of PP-IX solution. The comparison of survival curves indicates that this pigment extended the lifespan of CS. In contrast, Sod strain showed that the opposite effect and had no effect in Cat strain. The fact that PP-IX reduces the mean lifespan in Sod deficient strain might suggest a pro-oxidant action of PP-IX, and consequently the cumulating of ROS as a superoxide could have a mutagenic effect as was shown recently. The results presented evidence of the dual effect of PP-IX.

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Cellular communication and bystander effects: a critical review for modelling low-dose radiation action

Cited by 98 publications

References 44 publications

Lack of Bystander Effects from High-LET Radiation for Early Cytogenetic End Points

Lack of Bystander Effects from High-LET Radiation for Early Cytogenetic End Points

Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts

Action of protoporphyrin-IX (PP-IX) in the lifespan of <i>Drosophila melanogaster</i> deficient in endogenous antioxidants, Sod and Cat

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Cellular communication and bystander effects: a critical review for modelling low-dose radiation action

Cited by 98 publications

References 44 publications

Lack of Bystander Effects from High-LET Radiation for Early Cytogenetic End Points

Lack of Bystander Effects from High-LET Radiation for Early Cytogenetic End Points

Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts

Action of protoporphyrin-IX (PP-IX) in the lifespan of &lt;i&gt;Drosophila melanogaster&lt;/i&gt; deficient in endogenous antioxidants, Sod and Cat

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Action of protoporphyrin-IX (PP-IX) in the lifespan of <i>Drosophila melanogaster</i> deficient in endogenous antioxidants, Sod and Cat