Search results for "DNA DAMAGE"

A TDDFT-based Study on the Proton-DNA Collision

2019

The interaction of heavy charged particles with DNA is of interest for several areas, from hadrontherapy to aero-space industry. In this paper, a TD-DFT study on the interaction of a 4 keV proton with an isolated DNA base pair was carried out. Ehrenfest dynamics was used to study the evolution of the system during and after the proton impact up to about 193 fs. This time was long enough to observe the dissociation of the target, which occurs between 80-100 fs. The effect of base pair linking to the DNA double helix was emulated by fixing the four O3' atoms responsible for the attachment. The base pair tends to dissociate into its main components, namely the phosphate groups, sugars and nitr…

Cu(II) complexes with a sulfonamide derived from benzoguanamine. Oxidative cleavage of DNA in the presence of H2O2 and ascorbate

2004

Reaction between benzoguanamine (2,4-diamino-6-phenyl-1,3,5-triazine) and 2-mesitylenesulfonyl chloride leads to formation of a sulfonamide able to form two mononuclear Cu(II) complexes with a CuL(2) stoichiometry. The local environment of the metal cation is a distorted octahedron, with two ligands and two solvent molecules; both complexes crystallize in the monoclinic structure, space group P2(1), with Z=2. In the presence of ascorbate/H(2)O(2,) the two complexes significantly cleavage double-strand pUC18 DNA plasmid. Both complexes exhibit more nuclease efficiency that the copper phenantroline complex. From scavenging reactive oxygen studies we conclude that the hydroxyl radical and a si…

Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines

2013

It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure–activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methylharmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated fr…

Theoretical insight into the intrinsic ultrafast formation of cyclobutane pyrimidine dimers in UV-irradiated DNA: thymine versus cytosine.

2008

The higher formation yields measured in the ultrafast photoinduced formation of cyclobutane thymine dimers (T T) with respect to those of cytosine (C C) are explained, on the basis of ab initio CASPT2 results, by the existence in thymine of more reactive orientations and a less efficient photoreversibility, whereas in cytosine the funnel toward the photolesion becomes competitive with that mediating the internal conversion of the excited-cytosine monomer.

Activation of self-renewal and meiotic genes in tumour cell lines resistant to genotoxic treatment

2014

Pašatjaunošanās un meijotisko gēnu aktivācija pēc genotoksiskas apstrādes rezistentās audzēju šūnu līnijās Šajā darbā tika pētīta iespējamā saistība starp poliploīdijas un dzimumšūnu līnijai raksturīgo gēnu indukciju pēc pretvēža apstrādes atkarībā no TP53 statusa un audzēju šūnu rezistence pret DNS bojājumu. Pirmo reizi tika atrasta un citoloģiski raksturota galveno cilmestības transkripcijas faktoru OCT4, NANOG un SOX2 ekspresijas aktivācija, kas izraisīta pārkāpjot tetraploīdo barjeru pēc DNS bojājuma TP53 mutantās, bet ne funkcionālās audzēja šūnas, kā arī galvenā mejotiskā kohezīna REC8 ekspresija somatisko audzēja šūnu līnijās, kas apstrādātas ar jonizējošo starojumu vai topoizomeraze…

Photoinduced DNA Lesions in Dormant Bacteria: The Peculiar Route Leading to Spore Photoproducts Characterized by Multiscale Molecular Dynamics

2020

International audience; Some bacterial species enter a dormant state in the form of spores to resist to unfavorable external conditions. Spores are resistant to a wide series of stress agents, including UV radiation, and can last for tens to hundreds of years. Due to the suspension of biological functions, such as DNA repair, they accumulate DNA damage upon exposure to UV radiation. Differently from active organisms, the most common DNA photoproducts in spores are not cyclobutane pyrimidine dimers, but rather the so‐called spore photoproducts. This noncanonical photochemistry results from the dry state of DNA and its binding to small, acid‐soluble proteins that drastically modify the struct…

PARP inhibitor resistance induces massive genome alterations responsible of the acquisition of multidrug resistance in DNA damage repair-deficient pa…

2020

SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia

2014

SIRT1 is an important regulator of cellular stress response and genomic integrity. Its role in tumorigenesis is controversial. Whereas sirtuin 1 (SIRT1) can act as a tumor suppressor in some solid tumors, increased expression has been demonstrated in many cancers, including hematologic malignancies. In chronic myeloid leukemia, SIRT1 promoted leukemia development, and targeting SIRT1 sensitized chronic myeloid leukemia progenitors to tyrosine kinase inhibitor treatment. In this study, we investigated the role of SIRT1 in acute myeloid leukemia (AML). We show that SIRT1 protein, but not RNA levels, is overexpressed in AML samples harboring activating mutations in signaling pathways. In FMS-l…

Cytotoxicity, Genotoxicity and Disturbance of Cell Cycle in HepG2 Cells Exposed to OTA and BEA: Single and Combined Actions

2019

Mycotoxins are produced by a number of fungal genera spp., for example, Aspergillus, Penicillium, Alternaria, Fusarium, and Claviceps. Beauvericin (BEA) and Ochratoxin A (OTA) are present in various cereal crops and processed grains. This goal of this study was to determine their combination effect in HepG2 cells, presented for the first time. In this study, the type of interaction among BEA and OTA through an isobologram method, cell cycle disturbance by flow cytometry, and genotoxic potential by in vitro micronucleus (MN) assay following the TG 487 (OECD, 2016) of BEA and OTA individually and combined in HepG2 cells are presented. Cytotoxic concentration ranges studied by the MTT assay ov…

Exposure to UV radiation and risk of Hodgkin lymphoma: A pooled analysis

2013

Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320HLcasesand 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inv…