The inter-individual variability outperforms the intra-individual variability of differentially expressed proteins prior and post irradiation in lymphoblastoid cell lines

Guertler, Anne; Hauptmann, Monika; Pautz, S; Kulka, Ulrike; Friedl, Anna A.; Lehr, Stefan; Hornhardt, Sabine; Gomolka, Maria

doi:10.3109/13813455.2014.953548

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…The different number of DE genes between the RS and the RR cell line, 4 and 24 h after irradiation, indicates that the RS cell line was transcriptionally more active than the RR cell line in response to IR. This is in agreement with previous results where more differentially regulated proteins were detected in the RS cell line than in the RR one after irradiation 45 . Furthermore, many of the DE genes reported here are related to DNA damage and repair, regulation of cell cycle and apoptosis, processes known to be involved in radiation response 22 24 25 27 58 59 60 61 .…”

Section: Discussionsupporting

confidence: 94%

“…This is in agreement with previous results where more differentially regulated proteins were detected in the RS cell line than in the RR one after irradiation45. Furthermore, many of the DE genes reported here are related to DNA damage and repair, regulation of cell cycle and apoptosis, processes known to be involved in radiation response2224252758596061.…”

Section: Discussionsupporting

confidence: 93%

“…Variation in radiosensitivity can also be associated with differences in cell cycle regulation and apoptotic pathways 8 42 43 . In this sense, the two cell lines studied here are a good model given their previously reported different response to radiation 34 44 45 46 .…”

Section: Discussionmentioning

confidence: 85%

“…Characterisation of the two cell lines by M-FISH was carried out before irradiation and no chromosome aberrations were observed. Their radiosensitivity was previously tested 34 44 45 46 . According to this, one cell line (4060-200) was defined as RS and the other (20037-200) as RR.…”

Section: Methodsmentioning

confidence: 99%

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Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line

Borràs-Fresneda

Barquinero

Gomolka

et al. 2016

Sci Rep

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Normal tissue toxicity after radiotherapy shows variability between patients, indicating inter-individual differences in radiosensitivity. Genetic variation probably contributes to these differences. The aim of the present study was to determine if two cell lines, one radiosensitive (RS) and another radioresistant (RR), showed differences in DNA repair capacity, cell viability, cell cycle progression and, in turn, if this response could be characterised by a differential gene expression profile at different post-irradiation times. After irradiation, the RS cell line showed a slower rate of γ-H2AX foci disappearance, a higher frequency of incomplete chromosomal aberrations, a reduced cell viability and a longer disturbance of the cell cycle when compared to the RR cell line. Moreover, a greater and prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24 h after irradiation genes involved in “DNA damage response”, “direct p53 effectors” and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. The two cell lines showed different response to IR and can be distinguished with cell-based assays and differential gene expression analysis. The results emphasise the importance to identify biomarkers of radiosensitivity for tailoring individualized radiotherapy protocols.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line

Borràs-Fresneda

Barquinero

Gomolka

et al. 2016

Sci Rep

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“…Furthermore, the involvement of specific polymorphisms in breast, colorectal and lung cancer were reported [259][260][261]. The fact that γray exposure induces individual differences in proteomic profiles in human lymphoblastoid cell lines offers the possibility to develop proteomic biomarkers for individual IR responses [278].…”

Section: Biomarkers Relevant For Radiation Dosimetry and Biological Amentioning

confidence: 99%

Progress in low dose health risk research

Averbeck

Salomaa

Bouffler

et al. 2018

Mutation Research/Reviews in Mutation Research

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People are more often exposed to low as opposed to high doses of ionising radiation (IR). Knowledge on the health risks associated with exposures to ionising radiation above 100 mGy is quite well established, while lower dose risks are inferred from higher level exposure information (ICRP). The health risk assessments are mainly based on epidemiological data derived from the atomic bombing of Hiroshima and Nagasaki, medical exposure studies and follow-up studies after nuclear accidents. For the estimation of long-term stochastic radiation health effects (such as cancer) and radiation protection purposes, a linear non-threshold (LNT) model is applied. However, the general validity of the LNT hypothesis for extrapolations from effects of high to low doses (<100 mGy) and low dose-rates (<6 mGy/h) has been questioned as epidemiological studies are statistically limited at low doses and unable to evaluate low dose and low dose-rate health risks (UNSCEAR). Thus, uncertainties on health risks need to be clarified with the help of mechanistic studies. The European Network of Excellence DoReMi (2010-2016) was designed to address some of the existing uncertainties and to identify research lines that are likely to be most informative for low dose risk assessment. The present review reports the results obtained from studies addressing the induction of cancer and non-cancer effects by low dose IR as well as on individual radiation sensitivity. It is shown that low dose and low dose-rate effects are the result of complex network responses including genetic, epigenetic, metabolic and immunological regulation. Evidence is provided for the existence of nonlinear biological responses in the low and medium dose range as well as effects other than the classical DNA damage. Such effects may have a bearing on the quantitative and qualitative judgements on health effects induced by low dose radiations.

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Dynamic changes in the proteome of human peripheral blood mononuclear cells with low dose ionizing radiation

Nishad

Ghosh

2016

Mutation Research/Genetic Toxicology and Environmental Mutagene

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The inter-individual variability outperforms the intra-individual variability of differentially expressed proteins prior and post irradiation in lymphoblastoid cell lines

Abstract: The application of 2-D DIGE may offer a realistic chance for a better molecular characterization of radio-sensitivity and for the discovery of candidate biomarkers.

Cited by 7 publications

References 32 publications

Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line

Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line

Progress in low dose health risk research

Dynamic changes in the proteome of human peripheral blood mononuclear cells with low dose ionizing radiation

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