scholarly journals Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells

2011 ◽  
Author(s):  
Nicolaas Franken
Keyword(s):  
Cell Death ◽  
Relative Biological Effectiveness ◽  
Double Strand Breaks ◽  
Lung Tumour ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Biological Effectiveness ◽  
Reproductive Cell Death ◽  
High Linear Energy Transfer ◽  
Α Particles

scholarly journals Calculated relative biological effectiveness (RBE) for initial DNA double-strand breaks (DSB) from flattening filter and flattening filter-free 6 MV X-ray fields

BJR|Open ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 20200072
Author(s):  
Hisashi Nakano ◽  
Daisuke Kawahara ◽  
Satoshi Tanabe ◽  
Satoru Utsunomiya ◽  
Takeshi Takizawa ◽  
...  
Keyword(s):  
Relative Biological Effectiveness ◽  
Double Strand Breaks ◽  
Central Axis ◽  
X Rays ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Depth Measurement ◽  
Dna Dsbs ◽  
Flattening Filter ◽  
Biological Effectiveness

Objectives: We evaluated the radiobiological effectiveness based on the yields of DNA double-strand breaks (DSBs) of field induction with flattening filter (FF) and FF-free (FFF) photon beams. Methods: We used the particle and heavy ion transport system (PHITS) and a water equivalent phantom (30 × 30 × 30 cm3) to calculate the physical qualities of the dose-mean lineal energy (yD) with 6 MV FF and FFF. The relative biological effectiveness based on the yields of DNA-DSBs (RBEDSB) was calculated for standard radiation such as 220 kVp X-rays by using the estimating yields of SSBs and DSBs. The measurement points used to calculate the in-field yD and RBEDSB were located at a depth of 3, 5, and 10 cm in the water equivalent phantom on the central axis. Measurement points at 6, 8, and 10 cm in the lateral direction of each of the three depths from the central axis were set to calculate the out-of-field yD and RBEDSB. Results: The RBEDSB of FFF in-field was 1.7% higher than FF at each measurement depth. The RBEDSB of FFF out-of-field was 1.9 to 6.4% higher than FF at each depth measurement point. As the distance to out-of-field increased, the RBEDSB of FFF rose higher than those of FF. FFF has a larger RBEDSB than FF based on the yields of DNA-DSBs as the distance to out-of-field increased. Conclusions: The out-of-field radiobiological effect of FFF could thus be greater than that of FF since the spreading of the radiation dose out-of-field with FFF could be a concern compared to the FF. Advances in knowledge: The RBEDSB of FFF of out-of-field might be larger than FF.

A Role for DNA Double Strand Breaks in the Sensitivity of AML Cells to Clofarabine: Enhanced In Vitro Sensitivity in Primary AML Cells with FLT3 Mutations.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2582-2582
Author(s):  
Monica Pallis ◽  
Martin Grundy ◽  
Claire Seedhouse ◽  
Heather Pimblett ◽  
Nigel Russell
Keyword(s):  
Cell Death ◽  
Dna Synthesis ◽  
Cell Lines ◽  
Mitochondrial Membrane ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Cytochrome C Release ◽  
Strand Breaks ◽  
Flt3 Mutations ◽  
Kg1 Cells

Abstract Clofarabine is a purine nucleoside analogue which has been incorporated into several therapeutic trial protocols for the treatment of leukaemias including acute myeloid leukaemia (AML). The aims of the study are to ascertain mechanisms of clofarabine action in AML using cell lines and presentation samples from patients. We measured apoptosis by TdT assay, cytochrome C release and flow cytometric assays of the mitochondrial membrane potential probe DiOC6. To study the effects of clofarabine on DNA synthesis and DNA double strand breaks, we used bromodeoxyuridine (BrdU) and H2AX assays respectively. Equitoxic doses were established that caused approximately 20% cell death in the AML cell lines HL-60 (0.3 μM), KG1 (1 μM) and MV4.11 (1 μM) after 6 hours of continuous exposure. At these doses, clofarabine induced apoptotic DNA nicks, as measured by the TdT assay, and Cytochrome C release in all three cell lines. However, clofarabine-induced mitochondrial hyperpolarisation and depolarisation were found to be cell-type specific, occurring in HL-60 but not MV4.11 or KG1 cells, i.e. mitochondrial membrane depolarisation is not an essential part of the mechanism of clofarabine-induced apoptosis. Following clofarabine treatment, DNA synthesis was reduced by 91% within 1 hour in KG1 cells and by 80% in HL-60, but by only 9% in MV4.11. Out of the three cell lines, MV4.11 cells, which have a FLT3 internal tandem duplication (ITD), were the only ones to completely repair DNA double strand breaks following clofarabine removal. In 12 samples from patients with AML, the proportion of cells which incorporated BrdU in a 45 minute assay - a measure of the rate of cell cycling - differed considerably between samples, from 0.8% to 23%, median 13%. Cell death induced by clofarabine was correlated with the cycling rate of untreated cells (P=0.016). All 12 samples showed inhibition of DNA synthesis within 60 minutes of clofarabine treatment (range 20%–92% inhibition, median 54%). Mitochondrial membrane hyperpolarisation and depolarisation were not observed in patient cells. However, DNA double strand breaks were induced by clofarabine in patient cells. Paradoxically, i.e. in contrast to the results seen with the MV4.11 cell line, toxicity was greatest in samples with a FLT3 mutation (P=0.007). In conclusion, the FLT3 mutant MV4.11 cell line effectively repairs clofarabine-induced double strand breaks. Cell death in patient cells cultured with clofarabine is correlated with the presence of a FLT3 mutation. As we have previously established that AML samples with FLT3 mutations have upregulated DNA repair activity, this paradox might be explained by cycles of attempted DNA repair frustrated by renewed clofarabine incoporation into DNA, thus increasing the toxicity of the drug.

scholarly journals FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Kasper Fugger ◽  
Wai Kit Chu ◽  
Peter Haahr ◽  
Arne Nedergaard Kousholt ◽  
Halfdan Beck ◽  
...  
Keyword(s):  
Cell Death ◽  
Replication Stress ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks
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