HPRT mutations in V79 Chinese hamster cells induced by accelerated Ni, Au and Pb ions

Stoll, U.

doi:10.1080/095530096145283

Cited by 22 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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). This study also confirms the findings of Stoll et al (1995Stoll et al ( , 1996 who found an RBE for cell survival by high LET nickel ions (>1000 keV/μm) around 1.…”

Section: Cellular Survival After Heavy Ions Exposuresupporting

confidence: 89%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Cellular Survival After Heavy Ions Exposuresupporting

confidence: 89%

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

View full text Add to dashboard Cite

show abstract

“…For LETs above 900 keV/μm, RBE values for reproductive cell death dropped to 1 or below 1. Stoll et al ( 159 ) also found an RBE for inactivation by high LET lead ions (>10,000 keV/μm) far below 1 and for nickel ions (>1000 keV/μm) around 1. In a human neuronal progenitor cell line (Ntera2), the RBE max for apoptosis 48 h after iron ion exposure (1 GeV/n) was at least 3.4 ( 160 ).…”

Section: Influence Of Linear Energy Transfer On Transcription Factor mentioning

confidence: 92%

Transcription Factors in the Cellular Response to Charged Particle Exposure

et al. 2016

View full text Add to dashboard Cite

Charged particles, such as carbon ions, bear the promise of a more effective cancer therapy. In human spaceflight, exposure to charged particles represents an important risk factor for chronic and late effects such as cancer. Biological effects elicited by charged particle exposure depend on their characteristics, e.g., on linear energy transfer (LET). For diverse outcomes (cell death, mutation, transformation, and cell-cycle arrest), an LET dependency of the effect size was observed. These outcomes result from activation of a complex network of signaling pathways in the DNA damage response, which result in cell-protective (DNA repair and cell-cycle arrest) or cell-destructive (cell death) reactions. Triggering of these pathways converges among others in the activation of transcription factors, such as p53, nuclear factor κB (NF-κB), activated protein 1 (AP-1), nuclear erythroid-derived 2-related factor 2 (Nrf2), and cAMP responsive element binding protein (CREB). Depending on dose, radiation quality, and tissue, p53 induces apoptosis or cell-cycle arrest. In low LET radiation therapy, p53 mutations are often associated with therapy resistance, while the outcome of carbon ion therapy seems to be independent of the tumor’s p53 status. NF-κB is a central transcription factor in the immune system and exhibits pro-survival effects. Both p53 and NF-κB are activated after ionizing radiation exposure in an ataxia telangiectasia mutated (ATM)-dependent manner. The NF-κB activation was shown to strongly depend on charged particles’ LET, with a maximal activation in the LET range of 90–300 keV/μm. AP-1 controls proliferation, senescence, differentiation, and apoptosis. Nrf2 can induce cellular antioxidant defense systems, CREB might also be involved in survival responses. The extent of activation of these transcription factors by charged particles and their interaction in the cellular radiation response greatly influences the destiny of the irradiated and also neighboring cells in the bystander effect.

show abstract

“…The DNA solutions were desicated at room temperature. With a molecular mass of 667 g/mol per nucleotide pair and a plasmid size of 3199 base pairs, one can calculate the volume of a plasmid to be about 1.5×10 -5 µm 3 [5]. The sample contained 2.9×10 11 plasmid molecules.…”

Section: Ion Beam Irradiationmentioning

confidence: 99%

Formation of plasmid DNA strand breaks induced by low-energy ion beam: indication of nuclear stopping effects

Chen

Jiang

Youshan

et al. 1998

Radiation and Environmental Biophysics

View full text Add to dashboard Cite

Plasmid pGEM 3zf(+) was irradiated by nitrogen ion beam with energies between 20 and 100 keV and the fluence kept as 1x10(12)ions/cm2. The irradiated plasmid was assayed by neutral electrophoresis and quantified by densitometry. The yields of DNA with single-strand and double-strand breaks first increased then decreased with increasing ion energy. There was a maximal yield value in the range of 20-100 keV. The relationship between DNA double-strand breaks (DSB) cross-section and linear energy transfer (LET) also showed a peak-shaped distribution. To understand the physical process during DNA strand breaks, a Monte Carlo calculation code known as TRIM (Transport of Ions in Matter) was used to simulate energy losses due to nuclear stopping and to electronic stopping. It can be assumed that nuclear stopping plays a more important role in DNA strand breaks than electronic stopping in this energy range. The physical mechanisms of DNA strand breaks induced by a low-energy ion beam are also discussed.

show abstract

HPRT mutations in V79 Chinese hamster cells induced by accelerated Ni, Au and Pb ions

Cited by 22 publications

References 7 publications

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

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

Transcription Factors in the Cellular Response to Charged Particle Exposure

Formation of plasmid DNA strand breaks induced by low-energy ion beam: indication of nuclear stopping effects

Contact Info

Product

Resources

About