Transcriptional response of human cells to microbeam irradiation with 2.1MeV α-particles

Hellweg, Christine E.; Spitta, Luis F.; Arenz, Andrea; Bogner, Susanne; Ruscher, Roland; Baumstark‐Khan, Christa; Greif, Klaus-Dieter; Giesen, U.

doi:10.1016/j.asr.2007.03.028

Cited by 3 publications

(16 citation statements)

References 49 publications

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“…of 36 Ar (95 MeV/n, LET 272 keV/µm) were sufficient to have the similar effect (2 × NF-κB activation). The relative biological effectiveness for NF-κB activation (RBENF-κB) was also calculated, as mentioned in Section 4.7.3, and this is listed in Table 1.…”

Section: Effect Of Fluence On Nf-κb-dependent Dd-tdtomato Expressionmentioning

confidence: 91%

“…A clear difference in NF-κB activation was observed after 4 Gy of high-and low-LET radiation qualities. Among these different radiation qualities, NF-κB was activated by 36 Ar ions to a higher extent than by 12 C ions, 16 O ions, and X-rays. The activation of NF-κB did not follow a linear pattern above 8 Gy due to the increasing damaging capacity of heavy ions.…”

Section: Nf-κb-dependent Dd-tdtomato Expression After Exposure To Hea...mentioning

confidence: 97%

“…The Poisson distribution of the heavy ion hits in the cell nuclei was calculated according to Equation (3). Based on this, 44 hits of 16 O ions and 45 hits of 12 C ions per cell nucleus were required to double the NF-κB-dependent DD-tdTomato expression, whereas 3 hits of 36 Ar (95 MeV/n, LET 272 keV/µm) were sufficient to have the similar effect (2 × NF-κB activation). The relative biological effectiveness for NF-κB activation (RBE NF-κB ) was also calculated, as mentioned in Section 4.7.3, and this is listed in Table 1.…”

Section: Effect Of Fluence On Nf-κb-dependent Dd-tdtomato Expressionmentioning

confidence: 99%

“…The relative biological effectiveness for NF-κB activation (RBENF-κB) was also calculated, as mentioned in Section 4.7.3, and this is listed in Table 1. 36 Ar (LET 272 keV/µm), 12 C (LET 73 keV/µm), and 16 O (LET 51 keV/µm) ions. DD-tdTomato expression was determined by measuring the fluorescence intensity using flow cytometric analysis.…”

Section: Effect Of Fluence On Nf-κb-dependent Dd-tdtomato Expressionmentioning

confidence: 99%

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The Use of ProteoTuner Technology to Study Nuclear Factor κB Activation by Heavy Ions

Chishti

Baumstark‐Khan

Nisar

et al. 2021

IJMS

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Nuclear factor κB (NF-κB) activation might be central to heavy ion-induced detrimental processes such as cancer promotion and progression and sustained inflammatory responses. A sensitive detection system is crucial to better understand its involvement in these processes. Therefore, a DD-tdTomato fluorescent protein-based reporter system was previously constructed with human embryonic kidney (HEK) cells expressing DD-tdTomato as a reporter under the control of a promoter containing NF-κB binding sites (HEK-pNFκB-DD-tdTomato-C8). Using this reporter cell line, NF-κB activation after exposure to different energetic heavy ions (16O, 95 MeV/n, linear energy transfer—LET 51 keV/µm; 12C, 95 MeV/n, LET 73 keV/μm; 36Ar, 95 MeV/n, LET 272 keV/µm) was quantified considering the dose and number of heavy ions hits per cell nucleus that double NF-κB-dependent DD-tdTomato expression. Approximately 44 hits of 16O ions and ≈45 hits of 12C ions per cell nucleus were required to double the NF-κB-dependent DD-tdTomato expression, whereas only ≈3 hits of 36Ar ions were sufficient. In the presence of Shield-1, a synthetic molecule that stabilizes DD-tdTomato, even a single particle hit of 36Ar ions doubled NF-κB-dependent DD-tdTomato expression. In conclusion, stabilization of the reporter protein can increase the sensitivity for NF-κB activation detection by a factor of three, allowing the detection of single particle hits’ effects.

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Section: Effect Of Fluence On Nf-κb-dependent Dd-tdtomato Expressionmentioning

confidence: 91%

Section: Nf-κb-dependent Dd-tdtomato Expression After Exposure To Hea...mentioning

confidence: 97%

Section: Effect Of Fluence On Nf-κb-dependent Dd-tdtomato Expressionmentioning

confidence: 99%

Section: Effect Of Fluence On Nf-κb-dependent Dd-tdtomato Expressionmentioning

confidence: 99%

See 2 more Smart Citations

The Use of ProteoTuner Technology to Study Nuclear Factor κB Activation by Heavy Ions

Chishti

Baumstark‐Khan

Nisar

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In this research work, it has been determined that maximum biological efficiency lies in the range of ∼30 to 175 keV/μm and peaks around 90 keV/μm. For a wide range of mammalian cells including HEK cells, the RBE for cell killing reaches its maximum in this LET range (Antonovic et al, 2013;Hellweg et al, 2007b;Hu et al, 2014). At 100 keV/μm, average separation density between ionizing events from single hits roughly coincides with the DNA double helix diameter, i.e., 2 nm (20 Å) and has the greatest probability of causing a double-strand break which is the basis for most biologic effects (Hall and Hei, 2003).…”

Section: Cellular Survival After Heavy Ions Exposurementioning

confidence: 98%

Constitutive expression of tdTomato protein as a cytotoxicity and proliferation marker for space radiation biology

Chishti

Hellweg

Berger

et al. 2015

Life Sciences in Space Research

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The radiation risk assessment for long-term space missions requires knowledge on the biological effectiveness of different space radiation components, e.g. heavy ions, on the interaction of radiation and other space environmental factors such as microgravity, and on the physical and biological dose distribution in the human body. Space experiments and ground-based experiments at heavy ion accelerators require fast and reliable test systems with an easy readout for different endpoints. In order to determine the effect of different radiation qualities on cellular proliferation and the biological depth dose distribution after heavy ion exposure, a stable human cell line expressing a novel fluorescent protein was established and characterized. tdTomato, a red fluorescent protein of the new generation with fast maturation and high fluorescence intensity, was selected as reporter of cell proliferation. Human embryonic kidney (HEK/293) cells were stably transfected with a plasmid encoding tdTomato under the control of the constitutively active cytomegalovirus (CMV) promoter (ptdTomato-N1). The stably transfected cell line was named HEK-ptdTomato-N1 8. This cytotoxicity biosensor was tested by ionizing radiation (X-rays and accelerated heavy ions) exposure. As biological endpoints, the proliferation kinetics and the cell density reached 100 h after irradiation reflected by constitutive expression of the tdTomato were investigated. Both were reduced dose-dependently after radiation exposure. Finally, the cell line was used for biological weighting of heavy ions of different linear energy transfer (LET) as space-relevant radiation quality. The relative biological effectiveness of accelerated heavy ions in reducing cellular proliferation peaked at an LET of 91 keV/μm. The results of this study demonstrate that the HEK-ptdTomato-N1 reporter cell line can be used as a fast and reliable biosensor system for detection of cytotoxic damage caused by ionizing radiation.

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The Nuclear Factor κB pathway: A link to the immune system in the radiation response

Hellweg

2015

Cancer Letters

120

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Transcriptional response of human cells to microbeam irradiation with 2.1MeV α-particles

Cited by 3 publications

References 49 publications

The Use of ProteoTuner Technology to Study Nuclear Factor κB Activation by Heavy Ions

The Use of ProteoTuner Technology to Study Nuclear Factor κB Activation by Heavy Ions

Constitutive expression of tdTomato protein as a cytotoxicity and proliferation marker for space radiation biology

The Nuclear Factor κB pathway: A link to the immune system in the radiation response

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