The toxicity and DNA-damage mechanism of α-Fe2O3 nanoparticles

2016 ◽  
Vol 26 (2) ◽  
pp. 384-389
Author(s):  
Xiaoxing Wang ◽  
Yan Gu ◽  
Davidmark Johnson ◽  
Chuncheng Chen ◽  
Yingping Huang
2018 ◽  
Vol 124 ◽  
pp. 127-136 ◽  
Author(s):  
Qingpeng Wang ◽  
Xiaoxiao Tan ◽  
Zhifang Liu ◽  
Guoshuai Li ◽  
Ruiyan Zhang ◽  
...  

2021 ◽  
Vol 50 (1) ◽  
pp. 362-375
Author(s):  
Zhifang Liu ◽  
Zuojie Li ◽  
Tao Du ◽  
Yan Chen ◽  
Qingpeng Wang ◽  
...  

Dihydro-2-quinolone platinum(iv) hybrids exhibit effective antitumor activities by causing serious mitochondria injury and DNA damage, and show great potential in reversing cisplatin resistance and improving antitumor efficacies.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1195-1195
Author(s):  
Monica Pallis ◽  
Simone Clarke ◽  
Martin Grundy ◽  
Jaineeta Richardson ◽  
Dotun Ojo ◽  
...  

Abstract Abstract 1195 Cytogenetic abnormalities vary greatly in AML and those with gains and losses of chromosome parts, terminal deletions and whole chromosome losses could theoretically derive from telomere dysfunction. Cells with these abnormalities are characterised by telomere shortening and abnormal function characterised by activation of both the negative telomere regulator TRF1 and also of hTERT. The G quadruplex ligand RHPS4 (Pharminox Ltd, Biocity, Nottingham, UK) binds telomeres and induces DNA damage at higher doses in the short term and critical telomere shortening in longer term growth assays. We have previously reported cytostatic and cytotoxic effects for this agent in AML cell lines, whilst others have found that normal haematopoietic progenitor cells are not targeted. We have now examined effects of RHPS4 on the in vitro growth and survival of primary AML cells, comprising 9 samples with normal and 8 with abnormal karyotypes (5 complex, one -7, one 5q- and one with additional material on chromosomes 2 and 9). Cells were incubated with RHPS4 in standard 14 day colony assays and for 7 and 21 days in a novel suspension culture medium supplemented with supernatant from cultured normal human osteoblasts. In the 7 day cultures, no effects were observed on cell survival. In the longer term growth assays, a submicromolar IC50 for RHPS4 was observed in 7/8 samples with aberrant cytogenetics in contrast with only 1/9 with normal cytogenetics (P=0.003, Fisher's exact test). Furthermore, RHPS4 significantly sensitised samples with abnormal cytogenetics to daunorubicin reducing the median IC50 from 27nM to 10nM (n=8, p<0.05). A qPCR method was used to measure telomere length of untreated DNA from 15 of the samples; the qPCR assay had previously been performed in a separate patient cohort alongside a Southern technique and comparable values were attained for the two different methods. There were no significant differences in telomere lengths between the normal and abnormal cytogenetic groups suggestive that telomere length is not a determinant of RHPS4 sensitivity in these assays. Samples with adverse cytogenetics have previously been associated with an up-regulation of basal DNA damage markers and may therefore be sensitive to compounds that can exacerbate levels of damage. We therefore studied the levels of p-ATM by immunocytochemistry in RHPS4-treated cells and found a significant increase compared to untreated cells - hence RHPS4 may be acting via a DNA damage mechanism. We conclude that telomere targeting has exciting potential as therapy for a subset of AML patients including those with adverse cytogenetics who have a poor response to conventional chemotherapeutics. Disclosures: No relevant conflicts of interest to declare.


2018 ◽  
Vol 2018 (40) ◽  
pp. 4442-4451 ◽  
Author(s):  
Qingpeng Wang ◽  
Guoshuai Li ◽  
Zhifang Liu ◽  
Xiaoxiao Tan ◽  
Zhuang Ding ◽  
...  

Author(s):  
P.E. Champness ◽  
R.W. Devenish

It has long been recognised that silicates can suffer extensive beam damage in electron-beam instruments. The predominant damage mechanism is radiolysis. For instance, damage in quartz, SiO2, results in loss of structural order without mass loss whereas feldspars (framework silicates containing Ca, Na, K) suffer loss of structural order with accompanying mass loss. In the latter case, the alkali ions, particularly Na, are found to migrate away from the area of the beam. The aim of the present study was to investigate the loss of various elements from the common silicate structures during electron irradiation at 100 kV over a range of current densities of 104 - 109 A m−2. (The current density is defined in terms of 50% of total current in the FWHM probe). The silicates so far ivestigated are:- olivine [(Mg, Fe)SiO4], a structure that has isolated Si-O tetrahedra, garnet [(Mg, Ca, Fe)3Al2Si3AO12 another silicate with isolated tetrahedra, pyroxene [-Ca(Mg, Fe)Si2O6 a single-chain silicate; mica [margarite, -Ca2Al4Si4Al4O2O(OH)4], a sheet silicate, and plagioclase feldspar [-NaCaAl3Si5O16]. Ion- thinned samples of each mineral were examined in a VG Microscopes UHV HB501 field- emission STEM. The beam current used was typically - 0.5 nA and the current density was varied by defocussing the electron probe. Energy-dispersive X-ray spectra were collected every 10 seconds for a total of 200 seconds using a Link Systems windowless detector. The thickness of the samples in the area of analysis was normally 50-150 nm.


2004 ◽  
Vol 171 (4S) ◽  
pp. 416-416
Author(s):  
Tamer M. Said ◽  
Shyam Allamaneni ◽  
Kiran P. Nallella ◽  
Rakesh K. Sharma ◽  
Sijo J. Parekattil ◽  
...  

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