1,25-Dihydroxyvitamin D3 modulates effects of ionizing radiation (IR) on human keratinocytes: In vitro analysis of cell viability/proliferation, DNA-damage and -repair

2010 ◽  
Vol 121 (1-2) ◽  
pp. 324-327 ◽  
Author(s):  
Lea Trémezaygues ◽  
Markus Seifert ◽  
Thomas Vogt ◽  
Wolfgang Tilgen ◽  
Jörg Reichrath
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Cell Viability ◽  
Human Keratinocytes ◽  
Dihydroxyvitamin D3 ◽  
Dna Damage And Repair ◽  
1,25 Dihydroxyvitamin D3 ◽  
Vitro Analysis ◽  
In Vitro Analysis

scholarly journals In vitro analysis of the effect of Go Ark on Human Peripheral Blood Lymphocytes

2020 ◽  
Vol 11 (3) ◽  
pp. 410-414
Author(s):  
Daya Shankar Gautam ◽  
Prahlad Marskole ◽  
Saraswati Mishra ◽  
Nisha Tiwari ◽  
Anjali Kumari ◽  
...  
Keyword(s):  
Cell Viability ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes ◽  
The Difference ◽  
Vitro Analysis ◽  
In Vitro Analysis

Cow is worshiped in India as “Gomata” since ancient time. Its values have been signified in Vedas, Puranas & Ayurveda. Its urine/Go Ark is used in rituals & medicines traditionally in India. The Significance of Cow Urine has been studied by many workers. Now it is available in the market as distillate. Hence this study was designed to assess the potential of Fresh Go Ark (FGA) and Distillate Go Ark (DGA) on Human Peripheral blood lymphocytes (PBL) in Vitro using MTT Assay. It was found that FGA & DGA both had the potential to enhance the cell viability of Human PBL. FGA showed greater potential towards the enhancement of cell viability on Human PBL than that of DGA. However the difference between the impacts of FGA & DGA was not found to be significant when tested through Two way ANOVA.

scholarly journals Maintenance Therapy for ATM-Deficient Pancreatic Cancer by Multiple DNA Damage Response Interferences after Platinum-Based Chemotherapy

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2110
Author(s):  
Elodie Roger ◽  
Johann Gout ◽  
Frank Arnold ◽  
Alica K. Beutel ◽  
Martin Müller ◽  
...  
Keyword(s):  
Dna Damage ◽  
Maintenance Therapy ◽  
Dna Damage Response ◽  
Ductal Adenocarcinoma ◽  
Preclinical Trial ◽  
Platinum Based Chemotherapy ◽  
Damage Response ◽  
Vitro Analysis ◽  
In Vitro Analysis

Personalized medicine in treating pancreatic ductal adenocarcinoma (PDAC) is still in its infancy, albeit PDAC-related deaths are projected to rise over the next decade. Only recently, maintenance therapy with the PARP inhibitor olaparib showed improved progression-free survival in germline BRCA1/2-mutated PDAC patients after platinum-based induction for the first time. Transferability of such a concept to other DNA damage response (DDR) genes remains unclear. Here, we conducted a placebo-controlled, three-armed preclinical trial to evaluate the efficacy of multi-DDR interference (mDDRi) as maintenance therapy vs. continuous FOLFIRINOX treatment, implemented with orthotopically transplanted ATM-deficient PDAC cell lines. Kaplan–Meier analysis, cross-sectional imaging, histology, and in vitro analysis served as analytical readouts. Median overall survival was significantly longer in the mDDRi maintenance arm compared to the maintained FOLFIRINOX treatment. This survival benefit was mirrored in the highest DNA-damage load, accompanied by superior disease control and reduced metastatic burden. In vitro analysis suggests FOLFIRINOX-driven selection of invasive subclones, erased by subsequent mDDRi treatment. Collectively, this preclinical trial substantiates mDDRi in a maintenance setting as a novel therapeutic option and extends the concept to non-germline BRCA1/2-mutant PDAC.

scholarly journals High Levels of Intracellular Cysteine Promote Oxidative DNA Damage by Driving the Fenton Reaction

2003 ◽  
Vol 185 (6) ◽  
pp. 1942-1950 ◽  
Author(s):  
Sunny Park ◽  
James A. Imlay
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Physiological State ◽  
Dna Lesions ◽  
High Rate ◽  
Free Iron ◽  
Vitro Analysis ◽  
Permeable Iron ◽  
In Vitro Analysis

ABSTRACT Escherichia coli is generally resistant to H2O2, with >75% of cells surviving a 3-min challenge with 2.5 mM H2O2. However, when cells were cultured with poor sulfur sources and then exposed to cystine, they transiently exhibited a greatly increased susceptibility to H2O2, with <1% surviving the challenge. Cell death was due to an unusually rapid rate of DNA damage, as indicated by their filamentation, a high rate of mutation among the survivors, and DNA lesions by a direct assay. Cell-permeable iron chelators eliminated sensitivity, indicating that intracellular free iron mediated the conversion of H2O2 into a hydroxyl radical, the direct effector of DNA damage. The cystine treatment caused a temporary loss of cysteine homeostasis, with intracellular pools increasing about eightfold. In vitro analysis demonstrated that cysteine reduces ferric iron with exceptional speed. This action permits free iron to redox cycle rapidly in the presence of H2O2, thereby augmenting the rate at which hydroxyl radicals are formed. During routine growth, cells maintain small cysteine pools, and cysteine is not a major contributor to DNA damage. Thus, the homeostatic control of cysteine levels is important in conferring resistance to oxidants. More generally, this study provides a new example of a situation in which the vulnerability of cells to oxidative DNA damage is strongly affected by their physiological state.

scholarly journals Vibrational spectroscopy in sensing radiobiological effects: analyses of targeted and non-targeted effects in human keratinocytes

2016 ◽  
Vol 187 ◽  
pp. 213-234 ◽  
Author(s):  
Aidan D. Meade ◽  
Orla Howe ◽  
Valérie Unterreiner ◽  
Ganesh D. Sockalingum ◽  
Hugh J. Byrne ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Vibrational Spectroscopy ◽  
Human Keratinocytes ◽  
Mitogen Activated Protein Kinase ◽  
Low Doses ◽  
Damage Initiation ◽  
Damage Sensing ◽  
Radiobiological Effects

Modern models of radiobiological effects include mechanisms of damage initiation, sensing and repair, for those cells that directly absorb ionizing radiation as well as those that experience molecular signals from directly irradiated cells. In the former case, the effects are termed targeted effects while, in the latter, non-targeted effects. It has emerged that phenomena occur at low doses below 1 Gy in directly irradiated cells that are associated with cell-cycle-dependent mechanisms of DNA damage sensing and repair. Likewise in non-targeted bystander-irradiated cells the effect saturates at 0.5 Gy. Both effects at these doses challenge the limits of detection of vibrational spectroscopy. In this paper, a study of the sensing of both targeted and non-targeted effects in HaCaT human keratinocytes irradiated with gamma ray photons is conducted with vibrational spectroscopy. In the case of directly irradiated cells, it is shown that the HaCaT cell line does exhibit both hyperradiosensitivity and increased radioresistance at low doses, a transition between the two effects occurring at a dose of 200 mGy, and that cell survival and other physiological effects as a function of dose follow the induced repair model. Both Raman and FTIR signatures are shown to follow a similar model, suggesting that the spectra include signatures of DNA damage sensing and repair. In bystander-irradiated cells, pro- and anti-apoptotic signalling and mechanisms of ROS damage were inhibited in the mitogen-activated protein kinase (MAPK) transduction pathway. It is shown that Raman spectral profiles of bystander-irradiated cells are correlated with markers of bystander signalling and molecular transduction. This work demonstrates for the first time that both targeted and non-targeted effects of ionizing radiation damage are detected by vibrational spectroscopy in vitro.

scholarly journals In-vitro analysis of cell viability of an optimized tio2 bond-coat deposited by hvof for biomedical applications

2016 ◽  
Vol 4 ◽  
Author(s):  
Clavijo-Mej�a Germ�n ◽  
Espinosa-Arebel�z Diego ◽  
Rinc�n-L�pez July ◽  
Hermann-Mu�oz Jennifer ◽  
Giraldo-Betancur Astrid ◽  
...  
Keyword(s):  
Cell Viability ◽  
Bond Coat ◽  
Biomedical Applications ◽  
Vitro Analysis ◽  
In Vitro Analysis

1,25-Dihydroxyvitamin D3 and analogues protect primary human keratinocytes against UVB-induced DNA damage

2005 ◽  
Vol 78 (2) ◽  
pp. 141-148 ◽  
Author(s):  
Petra De Haes ◽  
Marjan Garmyn ◽  
Annemieke Verstuyf ◽  
Pierre De Clercq ◽  
Maurits Vandewalle ◽  
...  
Keyword(s):  
Dna Damage ◽  
Human Keratinocytes ◽  
Primary Human Keratinocytes ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3

The native structure of the eukaryotic ribosome

1983 ◽  
Vol 41 ◽  
pp. 432-433
Author(s):  
R.A. Milligan ◽  
P.N.T. Unwin
Keyword(s):  
Ribosomal Proteins ◽  
Crystal Form ◽  
Native Structure ◽  
X Ray Diffraction ◽  
Eukaryotic Ribosome ◽  
Vitro Analysis ◽  
In Vitro Analysis ◽  
Resolution Structure ◽  
Stable Unit

A detailed understanding of the mechanism of protein synthesis will ultimately depend on knowledge of the native structure of the ribosome. Towards this end we have investigated the low resolution structure of the eukaryotic ribosome embedded in frozen buffer, making use of a system in which the ribosomes crystallize naturally.The ribosomes in the cells of early chicken embryos form crystalline arrays when the embryos are cooled at 4°C. We have developed methods to isolate the stable unit of these arrays, the ribosome tetramer, and have determined conditions for the growth of two-dimensional crystals in vitro, Analysis of the proteins in the crystals by 2-D gel electrophoresis demonstrates the presence of all ribosomal proteins normally found in polysomes. There are in addition, four proteins which may facilitate crystallization. The crystals are built from two oppositely facing P4 layers and the predominant crystal form, accounting for >80% of the crystals, has the tetragonal space group P4212, X-ray diffraction of crystal pellets demonstrates that crystalline order extends to ~ 60Å.

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