Search results for "DNA DAMAGE"
showing 10 items of 534 documents
Expression of yeast but not human apurinic/apyrimidinic endonuclease renders Chinese hamster cells more resistant to DNA damaging agents.
1997
Abasic sites represent ubiquitous DNA lesions that arise spontaneously or are induced by DNA-damaging agents. They block DNA replication and are considered to be cytotoxic and mutagenic. The key enzymes involved in the repair of abasic sites are apurinic/apyrimidinic (AP) endonucleases which process these lesions in an error-free mechanism. To analyze the role of AP endonuclease in the protection of mammalian cells against DNA damaging agents, we have transfected both the human (APE) and the yeast (APN1) AP endonuclease in Chinese hamster cells and compared the effects of expression of these genes in stable transfectants as to survival of cells and formation of chromosomal aberrations. Alth…
DNA Oxidation Photoinduced by Norharmane Rhenium(I) Polypyridyl Complexes: Effect of the Bidentate N,N′-Ligands on the Damage Profile
2018
Re(I)--polypyridyl complexes have interesting and distinctive photochemical and photosensitizing properties. This work describes the capability to induce (or photoinduce) DNA damage of three Re(I)-complexes with a naturally occurring alkaloid called norharmane (nHo) as ligand: [Re(CO)₃ (nHo)(L)]CF₃ SO₃ where L=2,2'-bipyridine (ReBpy), phenanthroline (RePhen) or dipyrido[3,2-a:2',3'-c]phenazine (ReDppz). The interaction of the complexes with DNA was investigated by steady-state and time-resolved spectroscopy. Data show that the mode and strength of interaction depend on the chemical structure of the bidentate ligand. The complexes show a major static contribution to the overall interaction, …
Genotoxicity of six pesticides by Salmonella mutagenicity test and SOS chromotest.
1997
Abstract Two in vitro tests (Ames test and SOS chromotest), one for bacterial mutagenicity and one for primary DNA damage, were assayed to determine the genotoxic activity of 6 pesticides (atrazine, captafol, captan, chlorpyrifosmethyl, molinate and tetrachlorvinphos). Assays were carried out both in the absence and presence of S9 fractions of liver homogenate from rat (Sprague–Dawley) pretreated with Aroclor 1254. Captan and captafol were genotoxic on both the Ames test and the SOS chromotest. Comparisons with mutagenesis data in Salmonella indicated that the SOS assay detected as genotoxic the pesticides that were mutagenic on the Salmonella test. Non-genotoxic effects were not detected i…
Magnesium homeostasis and aging.
2010
Aging is very often associated with magnesium (Mg) deficit. Total plasma magnesium concentrations are remarkably constant in healthy subjects throughout life, while total body Mg and Mg in the intracellular compartment tend to decrease with age. Dietary Mg deficiencies are common in the elderly population. Other frequent causes of Mg deficits in the elderly include reduced Mg intestinal absorption, reduced Mg bone stores, and excess urinary loss. Secondary Mg deficit in aging may result from different conditions and diseases often observed in the elderly (i.e. insulin resistance and/or type 2 diabetes mellitus) and drugs (i.e. use of hypermagnesuric diuretics). Chronic Mg deficits have been…
DNA damage susceptibility and repair in correlation to calendric age and longevity.
2000
In two mouse strains, SAM P (senescence acceleration prone) and SAM R (senescence acceleration resistant), of different longevities, with a ratio of P/R=1:2), the DNA status in the course of aging has been investigated using the DNA Alkaline Filter Elution (AFE) technique. Six different organs (brain, liver, heart, lung, intestine, and muscle) have been used in each of the four animals of a given age. Earlier it had been shown, that DNA is damaged the more the higher the age of the animal. DNA damage susceptibility, measured after exposure of organ pieces to nitroquinoline-N-oxide (NQO), is also significantly increased at higher ages, while repair, measured of NQO damaged tissue after 3 h i…
Oxidative stress in environmental-induced carcinogenesis.
2009
Reactive oxygen species (ROS) are the more abundant free radicals in nature and have been related with a number of tissue/organ injuries induced by xenobiotics, ischemia, activation of leucocytes, UV exposition, etc. Oxidative stress is caused by an imbalance between ROS production and a biological system's ability to readily detoxify these reactive intermediates or easily repair the resulting damage. Thus, oxidative stress is accepted as a critical pathophysiological mechanism in different frequent human pathologies, including cancer. In fact ROS can cause protein, lipid, and DNA damage, and malignant tumors often show increased levels of DNA base oxidation and mutations. Different lifesty…
Age-associated DNA damage is accelerated in the senescence-accelerated mice
2000
We investigated how the DNA status correlates with the aging process in organisms, in different organs and in tissues using two inbred strains of mice, which are genetically related but have different senescence patterns. The SAMP1 mice belong to an accelerated senescence-prone and short lived strain, the other, SAMR1 mice are from an accelerated senescence-resistant and long lived strain. Using the alkaline filter elution technique, pieces of tissues from six organs: lung, intestine, liver, brain, muscle, and heart have been examined for DNA damage, mainly DNA single strand breaks. It was shown that in newborns the DNA damage is minimal, and it was increased significantly with calendric ag…
Lack of correlation between apoptosis and DNA single-strand breaks in X-irradiated human peripheral blood mononuclear cells in the course of ageing
1998
The dependence on age of both the basal and the X-radiation-induced levels of apoptosis was examined in human peripheral blood mononuclear cells (PBMC). In the same samples, the base value and the extent of induced DNA single-strand breaks were determined, using a sensitive and fast microplate assay. PBMC were isolated from blood of donors of various age groups (20-30, 40-60 and > 70 years of age) and X-irradiated ex vivo using a 6 MV linear accelerator to give a total exposure of 4 Gy. The mean basal levels of apoptosis in PBMC from donors in the 40-60 year age group and the > 70 year age group were found to be only slightly higher (by 20-10%) compared to that of the 20-30 year age group, …
Compromised nuclear envelope integrity drives tumor cell invasion
2020
AbstractWhile mutations leading to a fragile envelope of the cell nucleus are well known to cause diseases such as muscular dystrophies or accelerated aging, the pathophysiological consequences of the recently discovered mechanically induced nuclear envelope ruptures in cells harboring no mutation are less known. Here we show that repeated loss of nuclear envelope integrity in nuclei experiencing mechanical constraints promotes senescence in nontransformed cells, and induces an invasive phenotype including increased collagen degradation in human breast cancer cells, both in vitro and in a mouse xenograft model of breast cancer progression. We show that these phenotypic changes are due to th…
DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells.
2013
Recent studies have highlighted an apparently paradoxical link between self-renewal and senescence triggered by DNA damage in certain cell types. In addition, the finding that TP53 can suppress senescence has caused a re-evaluation of its functional role in regulating these outcomes. To investigate these phenomena and their relationship to pluripotency and senescence, we examined the response of the TP53-competent embryonal carcinoma (EC) cell line PA-1 to etoposide-induced DNA damage. Nuclear POU5F1/OCT4A and P21CIP1 were upregulated in the same cells following etoposide-induced G 2M arrest. However, while accumulating in the karyosol, the amount of OCT4A was reduced in the chromatin fract…