Candidate protein biomarkers as rapid indicators of radiation exposure

Horn, Simon; Rothkamm, Kai

doi:10.1016/j.radmeas.2011.02.001

Cited by 22 publications

(14 citation statements)

References 6 publications

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“…This suggests that while 53BP1 foci formation (32) and radiation-induced apoptosis (33) increase with ionizing radiation dose, it is known DSBs induce apoptosis through the activation of p53 through ATM phosphorylation (34,35). Therefore, maybe radiationinduced apoptosis at least partially independent of DSB formation.…”

Section: Discussionmentioning

confidence: 99%

Combined Analysis of Gamma-H2AX/53BP1 Foci and Caspase Activation in Lymphocyte Subsets Detects Recent and More Remote Radiation Exposures

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Combined Analysis of Gamma-H2AX/53BP1 Foci and Caspase Activation in Lymphocyte Subsets Detects Recent and More Remote Radiation Exposures

et al. 2013

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“…Rothkamm and Löbrich, ; Rothkamm et al, ; Kühne et al, ; Riballo et al, ]. As radiation‐induced γH2AX foci tend to co‐localise very reliably with 53BP1 and ATM‐pS1981, these other DNA damage response proteins can be used as alternative or, in situations where accuracy is of crucial importance, as additional markers of double‐strand breaks through co‐immunostaining [Ward et al, ; Bekker‐Jensen et al, ; Rothkamm et al, ; Horn and Rothkamm, ; Ojima et al, ]. Nonetheless, quantitative and spatio‐temporal inconsistencies in the relationship between foci and double‐strand breaks and heterogeneous foci dynamics within the nucleus have been reported and some of the underlying issues have been explored [Kinner et al, ; Costes et al, ; Barnard et al, ; Chiolo et al, ], at least for ionizing radiation.…”

Section: Dna Double‐strand Breaksmentioning

confidence: 99%

“…DNA damage foci, and especially γH2AX foci in peripheral white blood cells, are promising biomarkers in biological dosimetry where radiation exposures need to be estimated retrospectively [Rothkamm and Horn, ; Redon et al, , Roch‐Lefevre et al, ; Horn and Rothkamm, ; Horn et al, ]. This is largely due to the strong and reproducible dose response of radiation‐induced foci which enables foci yields to be converted to dose using a calibration curve.…”

Section: Radiation Exposure Assessmentmentioning

confidence: 99%

DNA damage foci: Meaning and significance

Rothkamm

Barnard

Moquet

et al. 2015

Environ and Mol Mutagen

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The discovery of DNA damage response proteins such as γH2AX, ATM, 53BP1, RAD51, and the MRE11/RAD50/NBS1 complex, that accumulate and/or are modified in the vicinity of a chromosomal DNA double-strand break to form microscopically visible, subnuclear foci, has revolutionized the detection of these lesions and has enabled studies of the cellular machinery that contributes to their repair. Double-strand breaks are induced directly by a number of physical and chemical agents, including ionizing radiation and radiomimetic drugs, but can also arise as secondary lesions during replication and DNA repair following exposure to a wide range of genotoxins. Here we aim to review the biological meaning and significance of DNA damage foci, looking specifically at a range of different settings in which such markers of DNA damage and repair are being studied and interpreted.

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“…There have been some significant efforts to improve throughput for some assays, such as by automating the sample flow for CBMN (Garty et al 2010; Turner et al 2011) or by simplifying the culturing and scoring techniques for CBMN (McNamee et al 2009; Fenech et al 2013; Romm et al 2013). Horn and Rothkamm (2011) suggested extending the number of days that Gamma-H2AX could be valid for dosimetry by combining protein bio-markers and examining the temporal patterns. Rothkamm et al (2013) compared four laboratories’ scoring after 2 and 24 h following irradiation and varying numbers of scored cells (20–50 cells) and found evidence that low and high doses could be discriminated with sufficient accuracy despite some inter-laboratory differences.…”

Section: Potential Means To Assess Dose For a Radiation Eventmentioning

confidence: 99%

Overview of the principles and practice of biodosimetry

Swartz

Flood

Williams

2014

Radiat Environ Biophys

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The principle of biodosimetry is to utilize changes induced in the individual by ionizing radiation to estimate the dose and, if possible, to predict or reflect the clinically relevant response, i.e., the biological consequences of the dose. Ideally, the changes should be specific for ionizing radiation, and the response should be unaffected by prior medical or physiological variations among subjects, including changes that might be caused by the stress and trauma from a radiation event. There are two basic types of biodosimetry with different and often complementary characteristics: those based on changes in biological parameters such as gene activation or chromosomal abnormalities and those based on physical changes in tissues (detected by techniques such as EPR). In this paper, we consider the applicability of the various techniques for different scenarios: small- and large-scale exposures to levels of radiation that could lead to the acute radiation syndrome and exposures with lower doses that do not need immediate care, but should be followed for evidence of long-term consequences. The development of biodosimetry has been especially stimulated by the needs after a large-scale event where it is essential to have a means to identify those individuals who would benefit from being brought into the medical care system. Analyses of the conventional methods officially recommended for responding to such events indicate that these methods are unlikely to achieve the results needed for timely triage of thousands of victims. Emerging biodosimetric methods can fill this critically important gap.

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Candidate protein biomarkers as rapid indicators of radiation exposure

Cited by 22 publications

References 6 publications

Combined Analysis of Gamma-H2AX/53BP1 Foci and Caspase Activation in Lymphocyte Subsets Detects Recent and More Remote Radiation Exposures

Combined Analysis of Gamma-H2AX/53BP1 Foci and Caspase Activation in Lymphocyte Subsets Detects Recent and More Remote Radiation Exposures

DNA damage foci: Meaning and significance

Overview of the principles and practice of biodosimetry

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