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ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells

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ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. / Burdak-Rothkamm, S; Short, S C; Folkard, M; Rothkamm, K; Prise, K M.

In: ONCOGENE, Vol. 26, No. 7, 15.02.2007, p. 993-1002.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Burdak-Rothkamm, S, Short, SC, Folkard, M, Rothkamm, K & Prise, KM 2007, 'ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells', ONCOGENE, vol. 26, no. 7, pp. 993-1002. https://doi.org/10.1038/sj.onc.1209863

APA

Burdak-Rothkamm, S., Short, S. C., Folkard, M., Rothkamm, K., & Prise, K. M. (2007). ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. ONCOGENE, 26(7), 993-1002. https://doi.org/10.1038/sj.onc.1209863

Vancouver

Burdak-Rothkamm S, Short SC, Folkard M, Rothkamm K, Prise KM. ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. ONCOGENE. 2007 Feb 15;26(7):993-1002. https://doi.org/10.1038/sj.onc.1209863

Bibtex

@article{575f5f0c40724b56ae236dd32dbbeea5,
title = "ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells",
abstract = "Radiotherapy is an important treatment for patients suffering from high-grade malignant gliomas. Non-targeted (bystander) effects may influence these cells' response to radiation and the investigation of these effects may therefore provide new insights into mechanisms of radiosensitivity and responses to radiotherapy as well as define new targets for therapeutic approaches. Normal primary human astrocytes (NHA) and T98G glioma cells were irradiated with helium ions using the Gray Cancer Institute microbeam facility targeting individual cells. Irradiated NHA and T98G glioma cells generated signals that induced gammaH2AX foci in neighbouring non-targeted bystander cells up to 48 h after irradiation. gammaH2AX bystander foci were also observed in co-cultures targeting either NHA or T98G cells and in medium transfer experiments. Dimethyl sulphoxide, Filipin and anti-transforming growth factor (TGF)-beta 1 could suppress gammaH2AX foci in bystander cells, confirming that reactive oxygen species (ROS) and membrane-mediated signals are involved in the bystander signalling pathways. Also, TGF-beta 1 induced gammaH2AX in an ROS-dependent manner similar to bystander foci. ROS and membrane signalling-dependent differences in bystander foci induction between T98G glioma cells and normal human astrocytes have been observed. Inhibition of ataxia telangiectasia mutated (ATM) protein and DNA-PK could not suppress the induction of bystander gammaH2AX foci whereas the mutation of ATM- and rad3-related (ATR) abrogated bystander foci induction. Furthermore, ATR-dependent bystander foci induction was restricted to S-phase cells. These observations may provide additional therapeutic targets for the exploitation of the bystander effect.",
keywords = "Astrocytes/metabolism, Ataxia Telangiectasia Mutated Proteins, Bystander Effect/radiation effects, Cell Cycle Proteins/genetics, Cell Line, Cell Line, Tumor, Coculture Techniques, Glioma/metabolism, Histones/biosynthesis, Humans, Phosphorylation, Protein-Serine-Threonine Kinases/genetics, S Phase/genetics, Signal Transduction/genetics",
author = "S Burdak-Rothkamm and Short, {S C} and M Folkard and K Rothkamm and Prise, {K M}",
year = "2007",
month = feb,
day = "15",
doi = "10.1038/sj.onc.1209863",
language = "English",
volume = "26",
pages = "993--1002",
journal = "ONCOGENE",
issn = "0950-9232",
publisher = "NATURE PUBLISHING GROUP",
number = "7",

}

RIS

TY - JOUR

T1 - ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells

AU - Burdak-Rothkamm, S

AU - Short, S C

AU - Folkard, M

AU - Rothkamm, K

AU - Prise, K M

PY - 2007/2/15

Y1 - 2007/2/15

N2 - Radiotherapy is an important treatment for patients suffering from high-grade malignant gliomas. Non-targeted (bystander) effects may influence these cells' response to radiation and the investigation of these effects may therefore provide new insights into mechanisms of radiosensitivity and responses to radiotherapy as well as define new targets for therapeutic approaches. Normal primary human astrocytes (NHA) and T98G glioma cells were irradiated with helium ions using the Gray Cancer Institute microbeam facility targeting individual cells. Irradiated NHA and T98G glioma cells generated signals that induced gammaH2AX foci in neighbouring non-targeted bystander cells up to 48 h after irradiation. gammaH2AX bystander foci were also observed in co-cultures targeting either NHA or T98G cells and in medium transfer experiments. Dimethyl sulphoxide, Filipin and anti-transforming growth factor (TGF)-beta 1 could suppress gammaH2AX foci in bystander cells, confirming that reactive oxygen species (ROS) and membrane-mediated signals are involved in the bystander signalling pathways. Also, TGF-beta 1 induced gammaH2AX in an ROS-dependent manner similar to bystander foci. ROS and membrane signalling-dependent differences in bystander foci induction between T98G glioma cells and normal human astrocytes have been observed. Inhibition of ataxia telangiectasia mutated (ATM) protein and DNA-PK could not suppress the induction of bystander gammaH2AX foci whereas the mutation of ATM- and rad3-related (ATR) abrogated bystander foci induction. Furthermore, ATR-dependent bystander foci induction was restricted to S-phase cells. These observations may provide additional therapeutic targets for the exploitation of the bystander effect.

AB - Radiotherapy is an important treatment for patients suffering from high-grade malignant gliomas. Non-targeted (bystander) effects may influence these cells' response to radiation and the investigation of these effects may therefore provide new insights into mechanisms of radiosensitivity and responses to radiotherapy as well as define new targets for therapeutic approaches. Normal primary human astrocytes (NHA) and T98G glioma cells were irradiated with helium ions using the Gray Cancer Institute microbeam facility targeting individual cells. Irradiated NHA and T98G glioma cells generated signals that induced gammaH2AX foci in neighbouring non-targeted bystander cells up to 48 h after irradiation. gammaH2AX bystander foci were also observed in co-cultures targeting either NHA or T98G cells and in medium transfer experiments. Dimethyl sulphoxide, Filipin and anti-transforming growth factor (TGF)-beta 1 could suppress gammaH2AX foci in bystander cells, confirming that reactive oxygen species (ROS) and membrane-mediated signals are involved in the bystander signalling pathways. Also, TGF-beta 1 induced gammaH2AX in an ROS-dependent manner similar to bystander foci. ROS and membrane signalling-dependent differences in bystander foci induction between T98G glioma cells and normal human astrocytes have been observed. Inhibition of ataxia telangiectasia mutated (ATM) protein and DNA-PK could not suppress the induction of bystander gammaH2AX foci whereas the mutation of ATM- and rad3-related (ATR) abrogated bystander foci induction. Furthermore, ATR-dependent bystander foci induction was restricted to S-phase cells. These observations may provide additional therapeutic targets for the exploitation of the bystander effect.

KW - Astrocytes/metabolism

KW - Ataxia Telangiectasia Mutated Proteins

KW - Bystander Effect/radiation effects

KW - Cell Cycle Proteins/genetics

KW - Cell Line

KW - Cell Line, Tumor

KW - Coculture Techniques

KW - Glioma/metabolism

KW - Histones/biosynthesis

KW - Humans

KW - Phosphorylation

KW - Protein-Serine-Threonine Kinases/genetics

KW - S Phase/genetics

KW - Signal Transduction/genetics

U2 - 10.1038/sj.onc.1209863

DO - 10.1038/sj.onc.1209863

M3 - SCORING: Journal article

C2 - 16909103

VL - 26

SP - 993

EP - 1002

JO - ONCOGENE

JF - ONCOGENE

SN - 0950-9232

IS - 7

ER -