Search results for "DNA DAMAGE"

Identification of Candidate Polymorphisms on Stress Oxidative and DNA Damage Repair Genes Related with Clinical Outcome in Breast Cancer Patients

2012

Diverse polymorphisms have been associated with the predisposition to develop cancer. On fewer occasions, they have been related to the evolution of the disease and to different responses to treatment. Previous studies of our group have associated polymorphisms on genes related to oxidative stress (rs3736729 on GCLC and rs207454 on XDH) and DNA damage repair (rs1052133 on OGG1) with a predisposition to develop breast cancer. In the present work, we have evaluated the hypothesis that these polymorphisms also play a role in a patient’s survival. A population-based cohort study of 470 women diagnosed with primary breast cancer and a median follow up of 52.44 months was conducted to e…

SYNTHESIS OF PYRROLO[3,2-H]QUINOLINONES WITH GOOD PHOTOCHEMOTHERAPEUTIC ACTIVITY AND NO DNA DAMAGE

2010

In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC₅₀ values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.

Heat shock protein Hsp70 expression and DNA damage in Baikalian sponges exposed to model pollutants and wastewater from Baikalsk Pulp and Paper Plant

2002

Abstract Lake Baikal, a unique habitat for a great number of endemic species, is the largest freshwater reservoir in the world which is still largely unaffected by anthropogenic pollution, except for some shore regions with industrial activity. The expressions of a biomarker of exposure (heat shock protein Hsp70) and a biomarker of effect (DNA single-strand breaks) were measured for the first time in endemic Baikalian sponge species (Baikalospongia intermedia, Lubomirskia fusifera, and Lubomirskia abietina). Tissue cubes of B. intermedia and dissociated cells of L. fusifera and L. abietina reacted to temperature stress (10–16 °C above ambient temperature) with a time-dependent increase in e…

The Role of DNA Damage in the Pathogenesis of Nitrate Tolerance

2013

DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol

2015

2-Methoxyestradiol (2-ME) is a physiological metabolite of 17β-estradiol. At pharmacological concentrations, 2-ME inhibits colon, breast and lung cancer in tumor models. Here we investigated the effect of physiologically relevant concentrations of 2-ME in osteosarcoma cell model. We demonstrated that 2-ME increased nuclear localization of neuronal nitric oxide synthase, resulting in nitro-oxidative DNA damage. This in turn caused cell cycle arrest and apoptosis in osteosarcoma cells. We suggest that 2-ME is a naturally occurring hormone with potential anti-cancer properties.

Induction of micronuclei in V79 Chinese hamster cells by tetrachlorohydroquinone, a metabolite of pentachlorophenol

1992

Tetrachlorohydroquinone, a metabolite of the fungicide pentachlorophenol, induced significant dose-related increases in micronuclei in V79 Chinese hamster cells without exogenous metabolic activation. The lowest observed effective dose was 10 microM, where the relative survival was about 62%. At the highest dose tested, 20 microM, the relative survival was about 8% and the frequency of cells with micronuclei was about 6 times the solvent control frequency. The induction of micronuclei by tetrachlorohydroquinone was significantly inhibited by the hydroxyl radical scavenger dimethyl sulfoxide at 5% (v/v).

Oxygen in the neonatal period: Oxidative stress, oxygen load and epigenetic changes

2020

Preterm infants frequently require positive pressure ventilation and oxygen supplementation in the first minutes after birth. It has been shown that the amount of oxygen provided during stabilization, the oxygen load, if excessive may cause hyperoxia, and oxidative damage to DNA. Epidemiologic studies have associated supplementation with pure oxygen in the first minutes after birth with childhood cancer. Recent studies have shown that the amount of oxygen supplemented to preterm infants after birth modifies the epigenome. Of note, the degree of DNA hyper-or hypomethylation correlates with the oxygen load provided upon stabilization. If these epigenetic modifications would persist, oxygen su…

Cytotoxic, immunomodulatory, antimycotic, and antiviral activities of semisynthetic 14-hydroxyabietane derivatives and triptoquinone C-4 epimers

2013

A series of C14-hydroxy derivatives of dehydroabietic acid were synthesised from commercial abietic acid and evaluated for their cytotoxic, antimycotic, and antiviral activities. From these C14-hydroxy derivatives, triptoquinone C-4 epimers were obtained and their immunomodulatory activity was additionally evaluated. None of the tested compounds showed antiviral activity against herpes simplex virus type 1 (HHV-1), and nor did they display antimycotic activity against certain Aspergillus, spp. except for one compound, abieta-8,11,13-trien-14,18-diol. Interestingly, two triptoquinone epimers showed cytotoxic activity, and one of them induced mitochondrial potential loss, DNA damage and cell …

Apaf-1 deficient mouse fibroblasts are resistant to MNNG and MMS-induced apoptotic death without attenuation of Bcl-2 decline.

2005

Abstract Simple alkylating agents induce cell death by activating the apoptotic pathway. In rodent fibroblasts, apoptosis triggered by DNA methylation lesions is executed via the mitochondrial damage pathway. Here, we studied cell death induced by the methylating agents methyl methanesulfonate (MMS) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in mouse fibroblasts wild-type (wt) and deficient for Apaf-1 (apaf-1 knockout cells). Apaf-1 is an essential component of the apoptosome complex that becomes activated upon cytochrome c release from mitochondria. We show that apaf-1 knockout cells are more resistant to the cytotoxic effect (as measured by WST assay) of methylating agents. This is d…

Photochemical and photobiological studies with acridine and phenanthridine hydroperoxides in cell-free DNA.

1997

The acridine and phenanthridine hydroperoxides 3 and 7 were synthesized as photochemical hydroxyl radical sources for oxidative DNA damage studies. The generation of hydroxyl radicals upon UVA irradiation (lambda = 350 nm) was verified by trapping experiments with 5,5-dimethyl-1-pyrroline N-oxide and benzene. The enzymatic assays of the damage in cell-free DNA from bacteriophage PM2 caused by the acridine and phenanthridine hydroperoxides 3 and 7 under near-UVA irradiation revealed a wide range of DNA modifications. Particularly, extensive single-strand break formation and DNA base modifications sensitive to formamidopyrimidine DNA glycosylase (Fpg protein) were observed. In the photooxidat…