Oxidative Dna Damage

Contradictory results exist in the literature about the antineoplastic activity of ferrocenes and their ferrocenium salts; additionally, little is known about the mechanism by which such drugs become active towards cancer cells. In the present paper we show that only ferrocenium species are able to inhibit the growth of Ehrlich ascites tumor cells in vivo and we propose that the cytotoxic activity of ferrocenium salts is not based on their direct linking to DNA, but on their ability to generate oxygen active species which induce oxidative DNA damage.

The need to understand and accurately assess the health risks of low dose ionizing radiation is more important now than ever before. The global applications of ionizing radiation in medicine, mining, manufacturing, and the nuclear industry have increased exponentially in recent years. Parallel to this increase are the health concerns regarding occupational and medical exposures to radiation. The research presented here investigates the biological and health effects of ionizing radiation, specifically from medical diagnostic exposures. Medical diagnostic procedures such as x-rays and computed tomography (CT) scans account for a notable portion of the public's exposure to ionizing radiation. The health risk to humans associated with these low dose exposures is unknown. Often times they are correlated with risk estimates derived from much higher radiation doses. There is no doubt that very high dose ionizing radiation can be harmful; however, the same notion does not exist regardi...

Biomarkers are used regularly in medical practice to provide objective markers of health status of a person, as well as the physiological response of the body to a pharmacological therapeutic intervention. In the specific case of the use of antioxidant products (antioxidant therapy), it is necessary to measure both biomarkers of oxidative stress level of the person as those that are specific to a physiological or pathological progression of a disease disorder. This paper describes the main biomarkers of oxidative general and specific stress as well as laboratory techniques, which should be taken into account when measuring the effectiveness of antioxidant therapies.

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Resumen

Los biomarcadores se utilizan de forma regular en la práctica médica para ofrecer marcadores objetivos del estado de salud de una persona, así como de la respuesta fisiológica del organismo a una intervención terapéutica farmacológica.  En el caso específico del uso de productos antioxidantes (terapia antioxidante) resulta necesario medir tanto biomarcadores del grado de estrés oxidativo de la persona como de aquellos que son específicos a un desorden fisiológico, patológico o la progresión de una enfermedad.  El presente trabajo describe los principales biomarcadores del estrés oxidativo, generales y específicos, así como las técnicas de laboratorio, que deben ser tomados en cuenta a la hora de medir la eficacia de las terapias antioxidantes.

This study confirms previous reports of the antiproliferative effect of OH–ferrocifen on both hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell models. Contrastive analysis of the proliferative effects of classical agonists (including estradiol and ethynylestradiol) and selective estrogen receptor modulators (SERMs) such as tamoxifen and its active metabolite, 4-hydroxy-tamoxifen, was also performed. Previous studies have attributed the effects of OH–ferrocifen on hormoneindependent cells to an underlying mechanism based on intracellular oxidation, production of hydroxyl radicals and oxidative damage of DNA. Here we report that the chemically generated OH–ferrocifen cation (as well as the decamethylferrocenium cation) is less cytotoxic to both cell lines than the neutral parent complex. Moreover, fluorescence activated cell sorting (FACS) analysis of 8-oxo-guanine production indicates that, even at relatively high concentrations, OH–ferrocifen produces negligible oxidative DNA damage as compared to other SERMs, namely tamoxifen and 4-hydroxy- amoxifen. Alternative pathways to explain the remarkable activity of OH–ferrocifen must therefore be sought.

Background Esophageal cancer has diverse incidence worldwide, and genetic/environmental risk factors are supposed to be responsible for it. OGG1 Ser326Cys gene polymorphism (rs1052133) has been found to be associated with different cancer susceptibilities and interaction with different environmental factors. Aim of the Study The aim of this study is to detect the role of OGG1 Ser326Cys polymorphism in susceptibility to esophageal cancer in two Northern Indian populations having different incidence rates. Methods A total of 737 cases and controls from two high and low at-risk populations were selected for the study. All the subjects were genotyped by PCR with confronting two-pair primers. Results No significant association was found between OGG1 Ser326Cys genotypes and esophageal cancer risk in both of the populations. Gene-environment analysis revealed no significant interaction between OGG1 Ser326Cys genotypes and smoking/high-salted tea intake habits. Conclusion OGG1 Ser326Cys polymorphism does not have a role in determining susceptibility to esophageal cancer either in high or in low at-risk populations of Northern India.

Abrin is a plant glycoprotein toxin, classified as ribosome inactivating protein (RIP) due to its property of damaging ribosomes in an irreversible manner. Many RIPs have direct DNA damaging activity. The objective of the present study was to evaluate the oxidative stress and DNA damaging potential of abrin in U937 human myeloleukemic cells. Cells were treated with abrin at IC50 of 8 ng/ml for 24h. Abrin induced a time dependent increase in reactive oxygen species and levels of antioxidant enzymes. There was significant depletion of reduced glutathione levels. DNA damage was assessed by comet assay in terms of percent head DNA, tail DNA, tail length and Olive tail moment. DNA damage was more pronounced at 4 and 8h at IC50 concentration. Abrin at 4, 8, 16 and 32 ng/ml concentration induced significant DNA damage at 4h. There was time dependent increase in levels of 8-OHdG in abrin treated cells indicating the oxidative stress mediated DNA damage. N-Acetylcysteine pretreatment at 10nM...

Genetic miscoding lesions can cause inaccuracies during the interpretation of ancient DNA sequence data. In this study, genetic miscoding lesions were identified and assessed by cloning and direct sequencing of degraded, amplified mitochondrial DNA (mtDNA) extracted from human remains. Forty-two individuals, comprising nine collections from five geographic locations, were analyzed for the presence of DNA damage that can affect the generation of a correct mtDNA profile. In agreement with previous studies, high levels (56.5% of all damage sites) of proposed hydrolytic damage products were observed. Among these, type 2 transitions (cytosine → thymine or guanine → adenine), which are highly indicative of hydrolytic deamination, were observed in 50% of all misincorporations that occurred. In addition to hydrolytic damage products, oxidative damage products were also observed in this study and were responsible for approximately 43.5% of all misincorporations. This level of misincorporation is in contrast to previous studies characterizing miscoding lesions from the analysis of bone and teeth, where few to no oxidative damage products were observed. Of all the oxidative damage products found in this study, type 2 transversions (cytosine → adenine/guanine → thymine or cytosine → guanine/guanine → cytosine), which are commonly formed through the generation of 8-hydroxyguanine, accounted for 30.3% of all genetic miscoding lesions observed. This study identifies the previously unreported presence of oxidative DNA damage and proposes that damage to degraded DNA templates is highly specific in type, correlating with the geographic location and the taphonomic conditions of the depositional environment from which the remains are recovered.

In the present study the chemopreventive effects of water soluble AquaROX(®) 15 and oil soluble VivOX(®) 40 rosemary extracts against 4-nitroquinoline-N-oxide (NQNO) and 2-amino-3-methyl-3H-imidazo[4,5-F]quinoline (IQ) induced mutagenicity in the reverse mutation assays with Salmonella typhimurium TA98 and against t-butyl hydroperoxide (t-BOOH), benzo(a)pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced DNA damage in HepG2 cells were studied, applying the comet assay. The results showed comparable protective effect of AquaROX and VivOX against oxidative DNA damage, whereas protection against indirect active genotoxic carcinogens was more efficient by VivOX.

Kajian ini telah dijalankan untuk mengkaji kerosakan oksidatif pada tikus aruhan diabetes melitus. Evaluasi aras kerosakan DNA dilakukan dengan kaedah Asai Komet Alkali menggunakan sel limfosit periferi yang diambil daripada darah tikus teraruh diabetes oleh streptozotocin ...

Oxidative DNA damage can be the consequence of endogenous metabolic processes and exogenous insults and several DNA repair enzymes provide protection against the toxic effects of oxidized DNA bases. Here we review the increasing knowledge on the relationship between an oxidized dNTPs pool and genome instability. The review also describes some important progress toward understanding the role of oxidative DNA damage and its repair in neurodegenerative diseases. In particular the hMTH1 hydrolase destroys oxidized nucleic acid precursors to prevent their harmful incorporation into DNA and RNA. Based on results obtained in our transgenic mouse overexpressing hMTH1 in the brain we discussed the mechanisms by which this hydrolase protects against neurodegeneration in Huntington disease models.

The effect of consumption of Brussels sprouts on the excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) into human urine was investigated. Ten non-smoking volunteers (five males and five females) were randomly assigned to two groups. Five volunteers started on a diet of 300 g of glucosinolate-free vegetables whereas the other five consumed 300 g of Brussels sprouts per day. After 1 week dietary