scholarly journals Assessment of DNA Damage after Photodynamic Therapy Using a Metallophthalocyanine Photosensitizer

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
A. El-Hussein ◽  
M. Harith ◽  
H. Abrahamse
Keyword(s):  
Dna Damage ◽  
Photodynamic Therapy ◽  
Adaptive Response ◽  
Uv Light ◽  
Cell Types ◽  
Surrounding Tissue ◽  
Target Tissue ◽  
X Rays ◽  
Integrity Of Dna ◽  
Mcf 7

Photodynamic therapy (PDT) is a chemotherapeutic approach that utilizes a bifunctional reagent, a photosensitizer (PS) that localizes to the target tissue relative to the surrounding tissue and is toxic when exposed to laser light. PDT rapidly induces cell death, inflammatory and immune reactions, and damage of the microvasculature. DNA damage results from a variety of factors including UV-light, X-rays, ionizing radiation, toxins, chemicals, or reactive oxygen species. The aim of this study was to determine the effect of PDT as well as the influence of presensitization leading to the adaptive response (AR) on the integrity of DNA. Lung (A549), breast (MCF-7), and esophageal (SNO) cancer cells and Zn sulfophthalocyanine as PS with irradiation conditions of 10 J/cm2at 636 nm were used. Subcellular localization of PS, cell morphology, and viability after PDT and DNA damage were determined. A significant decrease in viability and marked DNA damage was observed in all 3 cancer cell types in response to PDT while the adaptive response was demonstrated to significantly decrease the effectiveness of the PDT.

scholarly journals Radiation-induced DNA damage and repair effects on 3D genome organization

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacob T. Sanders ◽  
Trevor F. Freeman ◽  
Yang Xu ◽  
Rosela Golloshi ◽  
Mary A. Stallard ◽  
...  
Keyword(s):  
Dna Damage ◽  
Gene Expression Regulation ◽  
Genome Structure ◽  
Cell Types ◽  
Dimensional Structure ◽  
X Rays ◽  
3D Genome ◽  
Radiation Induced ◽  
The Impact ◽  
3D Genome Structure

AbstractThe three-dimensional structure of chromosomes plays an important role in gene expression regulation and also influences the repair of radiation-induced DNA damage. Genomic aberrations that disrupt chromosome spatial domains can lead to diseases including cancer, but how the 3D genome structure responds to DNA damage is poorly understood. Here, we investigate the impact of DNA damage response and repair on 3D genome folding using Hi-C experiments on wild type cells and ataxia telangiectasia mutated (ATM) patient cells. We irradiate fibroblasts, lymphoblasts, and ATM-deficient fibroblasts with 5 Gy X-rays and perform Hi-C at 30 minutes, 24 hours, or 5 days after irradiation. We observe that 3D genome changes after irradiation are cell type-specific, with lymphoblastoid cells generally showing more contact changes than irradiated fibroblasts. However, all tested repair-proficient cell types exhibit an increased segregation of topologically associating domains (TADs). This TAD boundary strengthening after irradiation is not observed in ATM deficient fibroblasts and may indicate the presence of a mechanism to protect 3D genome structure integrity during DNA damage repair.

scholarly journals Intermediate frequency magnetic field at 250.8 kHz does not induce DNA damage or “Adaptive Response” in vitro

2019 ◽  
Vol 3 (1) ◽  
pp. 42
Author(s):  
Zsuzsanna Németh ◽  
Erzsébet Laczkovich-Szaladják ◽  
Annamária Brech ◽  
Zsófia Szilágyi ◽  
Györgyi Kubinyi ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Adaptive Response ◽  
Cell Types ◽  
Intermediate Frequency ◽  
Magnetic Flux Density ◽  
Frequency Magnetic Field ◽  
Dna Strand

The aim of this study was to examine whether intermediate frequency (IF) magnetic field (MF) induces genotoxic effects or play a role in the induction of adaptive response after combined exposure to IF MF and ionizing radiation in leukocytes and in adrenocortical carcinoma cell line H295R. Cells were exposed to 250.8 kHz at the magnetic field strength of 80 A/m (equivalent to 100 µT magnetic flux density) for 20 hours alone, or exposed to IF MF for 20 hours and 24 hours later challenged with ionizing radiation (1.5 Gy X-ray). Evaluation of the DNA damage was performed with alkaline comet assay. Our results showed that there was no significant genotoxic effect of IF MF exposure compared to the controls in both cell types. Furthermore, results did not indicate a statistically significant change in DNA strand breaks in IF MF pre-exposed cells when they were subsequently exposed to 1.5 Gy. Consequently no adaptive response was detected.

scholarly journals Radiation-Induced DNA Damage and Repair Effects on 3D Genome Organization

2019 ◽  
Author(s):  
Jacob T. Sanders ◽  
Trevor F. Freeman ◽  
Yang Xu ◽  
Rosela Golloshi ◽  
Mary A. Stallard ◽  
...  
Keyword(s):  
Dna Damage ◽  
Gene Expression Regulation ◽  
Genome Structure ◽  
Cell Types ◽  
Dimensional Structure ◽  
X Rays ◽  
3D Genome ◽  
Radiation Induced ◽  
The Impact ◽  
3D Genome Structure

ABSTRACTThe three-dimensional structure of chromosomes plays an important role in gene expression regulation and also influences the repair of radiation-induced DNA damage. Genomic aberrations that disrupt chromosome spatial domains can lead to diseases including cancer, but how the 3D genome structure responds to DNA damage is poorly understood. Here, we investigate the impact of DNA damage response and repair on 3D genome folding using Hi-C experiments on wild type cells and ataxia telangiectasia mutated (ATM) patient cells. Fibroblasts, lymphoblasts, and ATM-deficient fibroblasts were irradiated with 5 Gy X-rays and Hi-C was performed after 30 minutes, 24 hours, or 5 days after irradiation. 3D genome changes after irradiation were cell type-specific, with lymphoblastoid cells generally showing more contact changes than irradiated fibroblasts. However, all tested repair-proficient cell types exhibited an increased segregation of topologically associating domains (TADs). This TAD boundary strengthening after irradiation was not observed in ATM deficient fibroblasts and may indicate the presence of a mechanism to protect 3D genome structure integrity during DNA damage repair.

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

Riboflavin and UV-Light Based Pathogen Reduction: Extent and Consequence of DNA Damage at the Molecular Level

2004 ◽  
Vol 80 (1) ◽  
pp. 15 ◽  
Author(s):  
Vijay Kumar ◽  
Owen Lockerbie ◽  
Shawn D. Keil ◽  
Patrick H. Ruane ◽  
Matthew S. Platz ◽  
...  
Keyword(s):  
Dna Damage ◽  
Molecular Level ◽  
Uv Light ◽  
Pathogen Reduction

The Structure and Photochromism of 2,4,4,6-Tetraphenyl-4H-thiopyran

1992 ◽  
Vol 57 (6) ◽  
pp. 1326-1334 ◽  
Author(s):  
Jaroslav Vojtěchovský ◽  
Jindřich Hašek ◽  
Stanislav Nešpůrek ◽  
Mojmír Adamec
Keyword(s):  
Solid State ◽  
Uv Light ◽  
Order Reaction ◽  
Boat Conformation ◽  
X Rays ◽  
Exponential Time ◽  
First Order ◽  
Double Plane ◽  
The Mean ◽  
Independent Molecules

2,4,4,6-Tetraphenyl-4H-thiopyran, C29H22S, orthorhombic, Pna21, a = 17.980(4), b = 6.956(2), c = 34.562(11) Å, V = 4323(2) Å3, Z = 8, Dx = 1.237 g cm-3, F(000) = 1696, λ(CuKα) = 1.54184 A, μ = 1.372 mm-2, T = 294 K. The final R was 0.050 for the unique set of 3103 observed reflections. The central 4H-thiopyran ring forms a boat conformation for both symmetrically independent molecules with average boat angles 4.4(3) and 6.8(3)° at S and C(sp3), respectively. The mean planes of phenyls at the position 2 and 6 are turned from the double plane of 4H-thiopyran by 42.5(5) and 35.8(3)°, respectively. The investigated material undergoes a photochromic change in the solid state after irradiation with UV light or X-rays. The maximum of the new absorption band is situated at 564 nm. The non-exponential time dependence of photochromic bleaching is analysed in terms of a dispersive first-order reaction.

scholarly journals Precisely Engineering a Carrier-free Hybrid Nanoassembly for Multimodal DNA Damage-augmented Photodynamic Therapy

2021 ◽  
pp. 130838
Author(s):  
Shumeng Li ◽  
Fujun Yang ◽  
Xinxin Sun ◽  
Yuequan Wang ◽  
Xuanbo Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Photodynamic Therapy ◽  
Carrier Free

scholarly journals Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Munetoshi Maeda ◽  
Masanori Tomita ◽  
Mika Maeda ◽  
Hideki Matsumoto ◽  
Noriko Usami ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Ataxia Telangiectasia ◽  
Kinase Inhibitor ◽  
Surrogate Marker ◽  
X Rays ◽  
Ataxia Telangiectasia Mutated ◽  
Whole Cell ◽  
X Ray ◽  
Dna Damage Responses

AbstractWe recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations. Addition of an ataxia telangiectasia mutated (ATM) kinase inhibitor to whole-cell irradiations suppresses foci formation at ≤ 2 Gy. ABL1 and p73 expression is upregulated following nucleus irradiation, suggesting the induction of p73-dependent cell death. Furthermore, CDKN1A (p21) is upregulated following whole-cell irradiation, indicating the induction of cell cycle arrest. These data reveal that cytoplasmic radioresponses modify ATM-mediated DNA damage responses and determine the fate of cells irradiated at low doses.

scholarly journals Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy

2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Meta Analysis ◽  
Protoporphyrin Ix ◽  
Cell Types ◽  
Amino Acid Derivative ◽  
Photodynamic Diagnosis

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

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