Medicine and Health Sciences Commons^™

Prognostic Significance Of Xct Polymorphisms And Expression In Patients With Advanced Pancreatic Cancer Treated With Chemotherapy, Tzu-Chuan Jane Huang Md

Dissertations & Theses (Open Access)

The plasma membrane x_c^- cystine/glutamate transporter mediates cellular uptake of cystine in exchange for intracellular glutamate and is highly expressed by pancreatic cancer cells. The xCT gene, encoding the cystine-specific xCT protein subunit of x_c^-, is important in regulating intracellular glutathione (GSH) levels, critical for cancer cell protection against oxidative stress, tumor growth and resistance to chemotherapeutic agents including platinum. We examined 4 single nucleotide polymorphisms (SNPs) of the xCT gene in 269 advanced pancreatic cancer patients who received first line gemcitabine with or without cisplatin or oxaliplatin. Genotyping was performed using Taqman real-time PCR …

Nitric Oxide-Mediated Inhibition Of Hdm2-P53 Binding, Christopher Schonhoff, Marie-Claire Daou, Stephen Jones, Celia Schiffer, Alonzo Ross

Celia A. Schiffer

It has become increasingly evident that nitric oxide exerts its effects, in part, by S-nitrosylation of cysteine residues. We tested in vitro whether nitric oxide may indirectly control p53 by S-nitrosylation and inactivation of the p53 negative regulator, Hdm2. Treatment of Hdm2 with a nitric oxide donor inhibits Hdm2-p53 binding, a critical step in Hdm2 regulation of p53. The presence of excess amounts of cysteine or dithiothreitol blocks this inhibition of binding. Moreover, nitric oxide inhibition of Hdm2-p53 binding was found to be reversible. Sulfhydryl sensitivity and reversibility are consistent with nitrosylation. Finally, we have identified a critical cysteine residue …

Insulin-Like Growth Factor 1 And Transforming Growth Factor-Β Stimulate Cystine/Glutamate Exchange Activity In Dental Pulp Cells, Katherine Pauly, Kymberly Fritz, Alyssa Furey, Doug Lobner

Biomedical Sciences Faculty Research and Publications

Introduction

The growth factors insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) are protective to dental pulp cells in culture against the toxicity of the composite materials Durafill VS and Flow Line (Henry Schein Inc, New York, NY). Because the toxicity of these materials is mediated by oxidative stress, it seemed possible that the protective effects of IGF-1 and TGF-β were through the enhancement of an endogenous antioxidant mechanism.

Methods

We used cultured dental pulp cells to determine the mechanism of the protective effects of IGF-1 and TGF-β, focusing on the glutathione system and the role of cystine/glutamate exchange …

Role Of Gsh Metabolism In Mediating Stromal-Leukemia Interaction And Promoting Cell Survival And Drug Resistance In Chronic Lymphocytic Leukemia, Wan Zhang

Dissertations & Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western countries. The interaction between CLL cells and the bone marrow stromal environment is thought to play a major role in promoting the leukemia cell survival and drug resistance. My dissertation works proved a novel biochemical mechanism by which the bone marrow stromal cells exert a profound influence on the redox status of primary CLL cells and enhance their ability to sustain oxidative stress and drug treatment. Fresh leukemia cells isolated from the peripheral blood of CLL patients exhibited two major redox alterations when they were cultured alone: …

Oxidative Stress Accumulates In Adipose Tissue During Aging And Inhibits Adipogenesis, Hannes M. Findeisen, Kevin J. Pearson, Florence Gizard, Yue Zhao, Hua Qing, Karrie L Jones, Dianne Cohn, Elizabeth B. Heywood, Rafael De Cabo, Dennis Bruemmer

Saha Cardiovascular Research Center Faculty Publications

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at …

Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu

All ETDs from UAB

Changes in the glioma microenvironment including oxygen (O2) levels, supply of amino acid such as L-glutamate and L-cystine and glutathione (GSH) concentrations play a critical role in glioma biology. Previous data from our laboratory and others have implicated the L-cystine/L-glutamate exchanger, system xc- in the invasion and proliferation of cancers including glioma. The central aim of this dissertation was to characterize the contribution of L-cystine uptake, GSH synthesis and L-glutamate release to migration and proliferation of glioma cells. In my first study, I examined the role of system xc- mediated L-glutamate release on glioma migration. I show that activation of …

S-Glutathionylation Activates Stim1 And Alters Mitochondrial Homeostasis., Brian J Hawkins, Krishna M Irrinki, Karthik Mallilankaraman, Yu-Chin Lien, Youjun Wang, Cunnigaiper D Bhanumathy, Ramasamy Subbiah, Michael F Ritchie, Jonathan Soboloff, Yoshihiro Baba, Tomohiro Kurosaki, Suresh K Joseph, Donald L Gill, Muniswamy Madesh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca(2+) signaling. However, precisely how oxidants influence Ca(2+) signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca(2+) mobilization from an oscillatory to a sustained elevated pattern via calcium release-activated calcium (CRAC)-mediated capacitive Ca(2+) entry, and stromal interaction molecule 1 (STIM1)- and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca(2+) entry alters mitochondrial Ca(2+) handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to …

Glutathione And Catalase Suppress Tgfß-Induced Cataract-Related Changes In Cultured Rat Lenses And Lens Epithelial Explants, Coral G. Chamberlain, Kylie J. Mansfield, Anna Cerra

Graduate School of Medicine - Papers (Archive)

Purpose: The damaging effects of oxidative stress and transforming growth factor-β (TGFβ)-induced transdifferentiation of lens epithelial cells have both been implicated independently in the etiology of cataract. The aim of this study was to investigate whether the presence of antioxidant systems in the lens influences the ability of lens epithelial cells to respond to TGFβ.

Methods: Whole lenses from young rats were cultured with or without TGFβ in the presence or absence of reduced glutathione (GSH). Lens epithelial explants from weanling rats were used to investigate the effects of GSH and catalase on TGFβ-induced cataract-related changes. Lenses were monitored for …

Manufactured Aluminum Oxide Nanoparticles Decrease Expression Of Tight Junction Proteins In Brain Vasculature, Lei Chen, Robert A. Yokel, Bernhard Hennig, Michal Toborek

Pharmaceutical Sciences Faculty Publications

Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular …

Trypanothione Reductase: A Viable Chemotherapeutic Target For Antitrypanosomal And Antileishmanial Drug Design, M. O. Faruk Khan

Pharmaceutical Science and Research

Trypanosomiasis and leishmaniasis are two debilitating disease groups caused by parasites of Trypanosoma and Leishmania spp. and affecting millions of people worldwide. A brief outline of the potential targets for rational drug design against these diseases are presented, with an emphasis placed on the enzyme trypanothione reductase. Trypanothione reductase was identified as unique to parasites and proposed to be an effective target against trypanosomiasis and leishmaniasis. The biochemical basis of selecting this enzyme as a target, with reference to the simile and contrast to human analogous enzyme glutathione reductase, and the structural aspects of its active site are presented. The …

Antioxidant Effect Of Zinc And Zinc-Metallothionein In The Acute Cytotoxicity Of Hydrogen Peroxide In Ehrlich Ascites Tumour Cells, Zacharias Suntres, Ed Lui

Edmund M. K. Lui

This study was concerned with the role of zinc (Zn) and zinc-metallothionein (Zn-MT) in oxidative stress. Hydrogen peroxide-induced oxidative injury was examined in Ehrlich ascites tumour cells isolated from control host mice, mice pretreated with 10 mg/kg ZnSO4 (i.p.) to increase cellular Zn/Zn-MT levels, and mice exposed to Zn-deficient diet to reduce the cellular Zn/Zn-MT levels. The results of the present study showed that Ehrlich cells with seven-fold differences in Zn-MT concentrations could be obtained by manipulating the Zn status of host mice and that high Zn and Zn-MT levels can make Ehrlich cells more resistant to H2O2-induced oxidative injury …

Rapid Determination Of Reduced And Oxidized Glutathione Levels Using A New Thiol-Masking Reagent And The Enzymatic Recycling Method: Application To The Rat Liver And Bile Samples, Imam H. Shaik, Reza Mehvar

Pharmacy Faculty Articles and Research

A microtiter plate assay for quantitation of reduced (GSH) and oxidized (GSSG) glutathione in the rat liver tissue and bile is described. The assay is based on the established enzymatic recycling method and a new thiol-masking reagent, 1-methyl-4-vinyl-pyridinium trifluoromethane sulfonate (M4VP). Samples were first processed by homogenization with (liver) or addition of (bile) sulfosalicylic acid. The total glutathione and GSSG were then determined before and after rapid (>= 2 min) and efficient (100%) masking of the GSH content of the samples with M4VP followed by the enzymatic recycling assay. The percentages of error and coefficient of variation of the …

Differential Effect Of Glutathione Depletion On Glycogenolysis In Isolated Rat Hepatocytes Mediated By A-Adrenoceptor Agonists And Glucagon, Mukadder Atmaca, Jeffrey R. Fry

Turkish Journal of Medical Sciences

Glutathione (GSH) exerts a variety of cytoprotecive effects, but is readily depleted from cells under a variety of stressful stimuli. The impact of GSH depletion on receptor-mediated activity in rat hepatocytes has been studied with regard to glycogenolysis stimulated with a-adrenoceptor agonists or glucagon, which exert their actions through different signalling pathways. Depletion of GSH content (70%) by diethyl maleate had no effect on the redox status of the cells or on basal or glucagon-stimulated glycogenolysis, but significantly reduced the response to the a-adrenoceptor agonists adrenalin and phenylephrine. These results highlight the possible modulatory effects of GSH on receptor-mediated activity …

Effects Of Defaunation And Urea On Glutathione And Malondialdehyde Levels In Blood And Ruminal Fluid Of Ramlıç Lambs, Yilmaz Dündar, Recep Aslan, Abdullah Eryavuz

Turkish Journal of Veterinary & Animal Sciences

The objective of this study was to investigate ruminal fluid and whole blood oxidant-antioxidant status in normal and fauna-free small ruminants. Forty male Ramlıç lambs, a local breed in the Afyon area, with an average body weight of 32-36 kg and approximately 210 days old were used. The lambs were divided equally into 4 groups (faunated (F), defaunated (D), faunated + urea (FU) and defaunated + urea (DU)). Malondialdehyde (MDA) and glutathione (GSH) concentrations in the ruminal fluid and blood were measured. In comparison with the controls, all parameters were significantly higher in the fauna-free animals. The ruminal fluid MDA …

Correlation Between Biochemical Parameters And Production Traits In Merino Crosses Sheep I- Erythrocyte Potassium And Glutathione, Ni̇hat Mert, Handan Gündüz, Vedat Akgündüz, Münevver Akgündüz

Turkish Journal of Veterinary & Animal Sciences

To determine the relationship between biochemical parameters and production traits in sheep, 111 sheep raised in Bandırma Sheep Research Institute were used as living material. Blood samples of 31 Hampshire Down x Merino, 33 Dorset Down x Merino, 27 German Black Headed x Merino and 20 Border Leicester x Merino crosses were taken. The levels and types of blood glutathione (GSH) and erythrocyte potassium (K^+) were determined. Correlations between some production traits such as greasy fleece weight and lamb birth weight were estimated. Statistical significance was found in greasy fleece weight and high glutathione (GSH^H) and low potassium (LK) SBA …

Investigation Of The Lipid Peroxidation, Antioxidant Substances, Antioxidant Vitamins And Some Hematologic-Biochemical Parameter Levels In Gentamycine Induced Nephrotoxicosis In Dogs, Ali̇ Erteki̇n, Mehmet Karaca, Hasan Altan Akkan, Mustafa Cemek, Nesli̇han Ormanci

Turkish Journal of Veterinary & Animal Sciences

In our study, malondialdehyde, antioxidant vitamins, antioxidant substances and some hematologic-biochemical parameter levels in nephrotoxicosis were investigated. Six dogs were used in the study. Blood samples taken before the experiment were used as the control. Blood samples were taken on days 2, 5, 7 and 10 during the experiment. During analysis, we found that the statistical changes were not significant in the retinol and Vitamin C levels of the experiment group when compared to those of the control group. \beta-carotene (P < 0.05) and Vitamin E (P < 0.001) levels were significantly decreased. Increases in the levels of malondialdehyde, seruloplasmin and urine \gamma-glutamyl transferase (GGT) enzyme were P < 0.001, while decreases in the amounts of glutathione were P < 0.001. We also found that changes in erythrocyte and hemotocrit levels were not significant. On the other hand, increases in the levels of leucocyte (P < 0.01), creatinin and blood urea nitrogen (BUN) P < 0.001 were significant. In conclusion, oxidative damage can occur in cells in nephrotoxicosis, the use of antioxidants could be of benefit during treatment with chemotherapeutics.

The Effect Of Long-Term Supplemental Dietary Cadmium On Lipid Peroxidation And The Antioxidant System In The Liver And Kidneys Of Rabbits, Ebru Beytut, Mesut Aksakal

Turkish Journal of Veterinary & Animal Sciences

We investigated the effects of chronic exposure to dietary cadmium (Cd) on the levels of lipid peroxidation (LPO) and reduced glutathione (GSH) associated with activities of glutathione peroxidase (GSH-Px) and the catalase (CAT) enzyme in the liver and kidneys of rabbits. Twenty 10-month-old clinically healthy New Zealand white rabbits (10/group) of 3545 ± 250 g average body weight were used. The control group was allowed to take food and tap water ad libitum, while the experimental group was given tap water containing 200 ppm CdCl_2/L for 28 weeks. Lipid peroxidation contents increased significantly in the liver (p < 0.001) and kidneys (p < 0.005) of Cd-treated rabbits. Glutathione levels decreased significantly in both the liver (p < 0.001) and the kidneys (p < 0.005) of the experimental group. Cadmium treatment caused a significant decrease in the activities of GSH-Px and CAT in the liver (p < 0.001, p < 0.01) and kidneys (p < 0.005, p < 0.1) of the rabbits. These results indicated that a Cd-induced increase in LPO was associated with reductions in GSH-Px and CAT enzyme activities, and in GSH levels in the liver and kidneys of rabbits.

The Radioprotective Effect Of Vitamins C, E And Vitamin E + Glutathione On The Small Intestine And The Thyroid Gland In Rats Irradiated With X- Rays, Cemi̇l Sert, M. Sali̇h Çeli̇k, Zülküf Akdağ, M. Aydin Ketani̇, Yusuf Nergi̇z

Turkish Journal of Medical Sciences

This investigation was carried out in order to determine the protective effects of long term administration at supraphysiologi- cal doses of vitamin E, vitamin C and a compound of vitamin E + glutathione against damage induced by free radicals produced by ionizing radiation. Five groups of 8-10-week-old Wistar albino rats were used in the study. Group I was the sham group and Group II was the radiation group (i.e. radiation alone). The rats in Group III were given a daily dose of 400 mg/kg of vit. C for one month. The rats in Group IV were given a daily dose …

The Effects Of Smoking On Glutathione Levels Inbronchoalveolar Lavage Fluid, Füsun Alataş, Necla Özdemi̇r, Özkan Alataş, Si̇nan Ergi̇nel, Muzaffer Meti̇ntaş, Rana Işik

Turkish Journal of Medical Sciences

Cigarette smoke contains high concentrations of oxidants and reactive oxygen species. The aim of this study was to evaluate the effect of long-term cigarette smoking on glutathione (GSH) levels in bronchoalveolar lavage (BAL) fluid. Nineteen current cigarette smokers and seven healthy nonsmoking volunteers were included in the study. BAL was performed by infusion of five sequential 20 ml aliquots and each aliquot was immediately aspirated. The levels of GSH were determined in BAL fluids. The epithelial lining fluid volume was calculated by the ratio of urea concentration in BAL fluid to that in serum. Lower GSH levels were observed in …

Oxidative Damage In Erythrocytes During Cold Storage With Organ Preservation Solution, Aki̇f B. Memmedoğlu, Ahmet Özaydin, İsmai̇l Seçki̇n, Gönül Sultuybek

Turkish Journal of Medical Sciences

It is known that erythrocyte aggregation in renal tissue during preserva-tion is cause of microcirculation defects in the reperfusion period. The aim of our study is to investigate oxidative damage in erythrocytes relative to the time of cold ischemia during organ preservation and relationship between lipid peroxidation and development of these damages. In experiments with a rabbit model, explanted kidneys were exposed to perfusion and 96 hours preservation with Euro-Collins (EC) in the 1st group, and University of Wisconsin (UW) solution in the 2nd group. Electron-microscopic examinations in renal tissueswere performed. Lipid peroxidation and glutathione levels in erythrocytes preserved in …

Overexpression Of Glyoxalase-I In Bovine Endothelial Cells Inhibits Intracellular Advanced Glycation Endproduct Formation And Prevents Hyperglycemia-Induced Increases In Macromolecular Endocytosis., Moritsugu Shinohara, P J. Thornalley, Ida Giardino, Paul Beisswenger, Suzanne R. Thorpe, Joelle Onorato, Michael Brownlee

Dartmouth Scholarship

Methylglyoxal (MG), a dicarbonyl compound produced by the fragmentation of triose phosphates, forms advanced glycation endproducts (AGEs) in vitro. Glyoxalase-I catalyzes the conversion of MG to S-D-lactoylglutathione, which in turn is converted to D-lactate by glyoxalase-II. To evaluate directly the effect of glyoxalase-I activity on intracellular AGE formation, GM7373 endothelial cells that stably express human glyoxalase-I were generated. Glyoxalase-I activity in these cells was increased 28-fold compared to neo-transfected control cells (21.80+/-0.1 vs. 0. 76+/-0.02 micromol/min/mg protein, n = 3, P < 0.001). In neo-transfected cells, 30 mM glucose incubation increased MG and D-lactate concentration approximately twofold above 5 MM (35.5+/-5.8 vs. 19.6+/-1.6, P < 0.02, n = 3, and 21.0+/-1.3 vs. 10.0+/-1.2 pmol/ 10(6) cells, n = 3, P < 0.001, respectively). In contrast, in glyoxalase-I-transfected cells, 30 mM glucose incubation did not increase MG concentration at all, while increasing the enzymatic product D-lactate by > 10-fold (18.9+/-3.2 vs. 18.4+/- 5.8, n = 3, P = NS, and 107.1+/-9.0 vs. 9.4+/-0 pmol/10(6) cells, n = …

Investigation Of Relationship Between Glutathione And Birth Weight And Liveweight Gain In Lambs, Ayşegül Bi̇ldi̇k, Fatmagül Yur, Hayati Çamaş, Fuat Odabaşioğlu, Mikail Aslan

Turkish Journal of Veterinary & Animal Sciences

This study was carried out to investigate the glutathione level in Morkaraman, Morkaraman x Dorsetdown (F1) and Morkaraman x Corriedale (F1) lambs and to demonstrate its relationship with birth-weight and live-weight gain. Fourtyone Morkaraman, 36 Morkaraman x Dorsetdown, 30 Morkaraman x Corriedale lambs were used as animal materials. Blood samples obtained from the animals were analysed by using spectrophotometric technique for the level of glutathione. In Morkaraman, Morkaraman x Dorsetdown and Morkaraman x Corriedale lambs, GSH h levels were 17.7±1.1, 19.9±0.9, 18.6±1.7 mg/dl respectivels and GSH H levels were 40.3±2.2, 36.2±1.9, 31.1±0.9 mg/dl respectively. Relationship between birth-weight and GSH level …

The Change Of Glutathione Dependentanti-Oxidant Mechanism In Patients With Chronicrenal Disease By Hemodialysis, Hatice Paşaoğlu, Sabahattin Muhtaroğlu, Mehmet Güneş, Cengiz Utaş

Turkish Journal of Medical Sciences

In order to test the for existence of a possible effect during hemodialysis we investigated glutathione and related enzymes before and after dialysis of 36 patients (20 M/16 F) with chronic renal failure (CRF). 25 healthy person (15 M/10F) served as controls. Erythrocyte reduced glutathione (GSH) concentrations, glucose -6- phosphate dehydrogenase (G-6-PD), glutathione peroxidase (GPX) activities and plasma GPX activities were significantly decreased in patients (p

Asbestos Induces Nuclear Factor Kappa B (Nf-Kappa B) Dna-Binding Activity And Nf-Kappa B-Dependent Gene Expression In Tracheal Epithelial Cells., Yvonne M. Janssen, Aaron Barchowsky, Melinda Treadwell, Kevin E. Driscoll, B T. Mossman

Dartmouth Scholarship

Nuclear factor kappa B (NF-kappa B) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation--features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-kappa B-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-kappa B-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced …

Depletion Of Glutathione And Enhanced Lipid Peroxidation In The Csf Of Acute Psychotics Following Haloperidol Administration., B. Nagesh Pai, N. Janakiramaih, B. N. Gangadhar, Vijayalakshmi Ravindranath

Graduate School of Medicine - Papers (Archive)

Haloperidol administration for 2 weeks results in significant reduction in the concentration of GSH in the CSF. Concomitantly, the levels of lipid peroxidation products increased as evidenced by increased malondialdehyde levels. The malondialdehyde levels in the CSF prior to haloparidol administration were not significantly higher than that seen in CSF from normal controls (data not shown) suggesting that increased oxidative stress did not exist in these patients prior to haloperidol administration. All the patients included in the present study were drug naive and hence the changes observed in the glutathione and malon6ialdehyde levels in the CSF were indeed mediated by …

Oncolog, Volume 39, Number 01 January-March 1994, Sunita Patterson, Maureen E. Goode, Kathryn L. Hale

OncoLog MD Anderson's Report to Physicians (All issues)

• Liposomal muramyl tripeptide kills bone cancer cells by stimulating the immune system Gene therapy at M. D. Anderson
• Researcher studies the hemopreventive power of garlic

Modulation Of Cisplatin Sensitivity And Growth Rate Of An Ovarian Carcinoma Cell Line By Bombesin And Tumor Necrosis Factor-Alpha., Seiji Isonishi, Antti P. Jekunen, Doreen K. Hom, Alan Eastman, Peter S. Edelstein, Franz B. Thiebaut, Randolph D. Christen, Stephen B. Howell

Dartmouth Scholarship

A twofold change in the cisplatin (DDP) sensitivity of 2008 human ovarian carcinoma cells is sufficient to reduce tumor response in vivo. The DDP sensitivity of these cells can be enhanced by activation of the epidermal growth factor and protein kinase C signal transduction pathways. We report here that two endogenous growth factors, bombesin and tumor necrosis factor alpha (TNF alpha), enhanced DDP sensitivity by factors of 1.7 +/- 0.1 (SD)-fold and 1.8 +/- 0.1 (SD)-fold, respectively. Both agents also produced sensitization in an 11-fold DDP-resistant 2008 subline. Neither bombesin nor TNF alpha changed the accumulation of DDP, glutathione content, …

Reaction Of Chromium(Vi) With Glutathione Or With Hydrogen Peroxide: Identification Of Reactive Intermediates And Their Role In Chromium(Vi)-Induced Dna Damage, J Aiyar, H Berkovits, R Floyd, K Wetterhahn

Dartmouth Scholarship

The types of reactive intermediates generated upon reduction of chromium(VI) by glutathione or hydrogen peroxide and the resulting DNA damage have been determined. In vitro, reaction of chromium(VI) with glutathione led to formation of two chromium(V) complexes and the glutathione thiyl radical. When chromium(VI) was reacted with DNA in the presence of glutathione, chromium-DNA adducts were obtained, with no DNA strand breakage. The level of chromium-DNA adduct formation correlated with chromium(V) formation. Reaction of chromium(VI) with hydrogen peroxide led to formation of hydroxyl radical. No chromium(V) was detectable at 24 degrees C (297 K); however, low levels of the tetraperoxochromium(V) …