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Mutagenic Effects (mutagenic + effects)
Selected AbstractsDeficiency in OGG1 Protects against Inflammation and Mutagenic Effects Associated with H. pylori Infection in MouseHELICOBACTER, Issue 5 2006Eliette Touati Abstract Background:,Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory and genotoxic host response to the infection. Materials and Methods:, Big Blue Ogg1,/, C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild-type (Wt) context. Results:, Inflammatory lesions induced in the gastric mucosa of H. pylori -infected mice, corresponding to a moderate gastritis, were less severe in Ogg1,/, than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1,/, than in the Wt mice. In these conditions, the H. pylori -SS1 infection in the Ogg1,/, mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months. Conclusions:, The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection. [source] Comparative mutagenic effects of structurally similar flavonoids quercetin and taxifolin on tester strains Salmonella typhimurium TA102 and Escherichia coli WP-2 uvrAENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2009Patrudu S. Makena Abstract Quercetin (QT) and Taxifolin (TF) are structurally similar plant polyphenols. Both have been reported to have therapeutic potential as anti-cancer drugs and antioxidants. Mutagenic effects of QT and TF were evaluated using Salmonella typhimurium TA102 and Escherichia coli WP-2 uvrA tester strains. Either in the presence or absence of S9 mix, QT was mutagenic to TA102 and WP2 uvrA. However, the mutagenicity of QT was significantly enhanced in the presence of S9 mix. Likewise, in the presence of Iron (Fe2+) and NADPH generating system (NGS) and absence of S9 mix, QT induced significantly high mutations in both TA102 and WP-2 uvrA. Mutagenicity of QT decreased in both strains in the presence of Iron (Fe2+) or NGS alone. TF was not mutagenic in the presence or absence of S9 mix in both TA102 and WP-2 uvrA 2, regardless of the presence of iron or NGS. Incorporation of antioxidants (ascorbate, superoxide dismutase (SOD), catalase (CAT)) and/or iron chelators (desferroxamine (DF) and ethylenediamine-tetraacetate (EDTA)) in the test systems markedly decreased QT-induced mutations in both tester strains. These results suggest that QT but not TF, could induce mutations in the presence or absence of rat liver S9 or Iron (Fe2+) and NGS in both tester strains by redox cycling and Fenton reactions to produce oxygen free radicals. Our results indicate that a minor structural variation between the two plant polyphenols could elicit a marked difference in their genotoxicities. These results provide a basis for further study into the potential use of QT in combination with iron supplements. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source] Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of human lymphoblastoid cells or in utero exposure of CD-1 mice to single agents or drug combinations,,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3-4 2007Salina M. Torres Abstract Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using cell cloning assays for assessing the effects of individual drugs/drug combinations in (1) TK6 human lymphoblastoid cells exposed in vitro and (2) splenic lymphocytes from male CD-1 mice exposed transplacentally on days 12,18 of gestation. In TK6 cells, dose-related increases in HPRT and TK mutant frequencies were found following 3 days of exposure to AZT or 3TC alone (33, 100, or 300 ,M), or to equimolar amounts of AZT-3TC. Compared with single drug exposures, AZT-3TC coexposures generally yielded enhanced elevations in HPRT and TK mutant frequencies. Mutagenicity experiments with ABC alone, or in combination with AZT-3TC, were complicated by the extreme cytotoxicity of ABC. Exposure of cells either to relatively high levels of AZT-3TC short-term (100 ,M, 3 days), or to peak plasma-equivalent levels of AZT-3TC for an extended period (10 ,M, 30 days), resulted in similar drug-induced mutagenic responses. Among sets of mice necropsied on days 13, 15, or 21 postpartum, Hprt mutant frequencies in T-cells were significantly elevated in the AZT-only (200 mg/kg bw/day) and AZT-3TC (200 mg AZT + 100 mg 3TC/kg bw/day) groups at 13 days of age. These results suggest that the mutagenicity by these nucleoside analogs is driven by cumulative dose, and raises the question of whether AZT-3TC has greater mutagenic effects than AZT alone in perinatally exposed children. Environ. Mol. Mutagen. © 2007 Wiley-Liss, Inc. [source] Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary adenocarcinomas in Syrian golden hamsters contain beta 2-adrenergic receptor single-nucleotide polymorphismsGENES, CHROMOSOMES AND CANCER, Issue 2 2005Thomas Masi Cigarette smoking contributes to the development of lung cancer throughout the world, with cases of pulmonary adenocarcinoma (PAC) the most numerous. Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is formed from nicotine, has been demonstrated to cause mutations in genes that affect cell regulation and proliferation. Moreover, NNK has been shown to interact directly with and stimulate beta adrenergic receptor (ADRB) signal transduction pathways. Our goal was to determine whether single-nucleotide polymorphisms (SNPs) in the Adrb2 from PAC tumors were induced in golden hamsters by the injection of NNK. Here we report the cloning and sequencing of Adrb2 clones from either dissected lung tumors from NNK-injected animals or whole-lung tissue from water-injected controls. Both sets of animals contained SNPs; however, we found significantly more SNPs in the Adrb2 from NNK-injected animals than in the controls. The majority of these SNPs were novel, nonsynonymous mutations found in regions of the Adrb2 known to be involved in ligand binding, G-protein coupling, and desensitization/down-regulation. Our data verified the mutagenic effects of NNK as well as demonstrated that this animal model provides an outstanding way of identifying mutations not only in the Adrb2, but also in other genes that may play essential roles in the regulation and growth of pulmonary adenocarcinomas. © 2005 Wiley-Liss, Inc. [source] Examination of cytotoxicity and mutagenicity of AH26 and AH Plus sealersINTERNATIONAL ENDODONTIC JOURNAL, Issue 5 2003I. Mileti Abstract Aim ,To study in vitro the cytotoxic and mutagenic effects of AH26 and AH Plus. Methodology ,Cytotoxic effects on Chinese hamster V79 cells were determined by counting viable cells following incubation with eluations of AH26 and AH Plus. In one set of experiments, the materials were mixed, set for 1 h and then eluted with dimethyl sulphoxide (DMSO) for 1 h, 24 h and 7 days. In the other set, AH26 and AH Plus were mixed and set for 1 h, 24 h and 7 days in physiological saline then crushed and eluted in DMSO for 24 h. The cytotoxic effects of these eluates were evaluated. Three concentrations were chosen to examine the mutagenic effects of AH26 and AH Plus: 5.57, 16.7 and 55.7 ,g mL,1. The structural chromosomal aberration analysis and micronucleus test were performed on human lymphocytes according to standard procedures. Results ,Dose,response curves of cell survival were obtained. Both materials were shown to be cytotoxic in doses larger than 55.7 ,g mL,1, except for AH26, after 7 days setting time. AH Plus was also shown to be toxic in concentrations of 16.7 ,g mL,1, except after 7 days setting time. Neither AH26 nor AH Plus induced a significant increase of chromosomal aberrations or micronuclei induction at any setting time or concentration. Conclusion ,There was no mutagenicity found for AH26 and AH Plus on human lymphocytes in highly controlled conditions in vitro. [source] Absence of mutagenic effects of a particular Symphytum officinale L. liquid extract in the bacterial reverse mutation assayPHYTOTHERAPY RESEARCH, Issue 3 2010Birgit Benedek Abstract Comfrey (Symphytum officinale L.) root is traditionally used for the topical treatment of contusions, strains and sprains. Besides allantoin and rosmarinic acid, which are discussed as pharmacologically active principles, the drug contains pyrrolizidine alkaloids (PAs) known for their hepatotoxic, carcinogenic and mutagenic properties. The topical herbal medicinal products Kytta-Salbe® f and Kytta-Plasma® f contain a PA-free liquid extract from comfrey root as active substance. The aim of this study was to demonstrate the absence of genotoxic effects of this special extract in the bacterial reverse mutation assay (Ames test). Briefly, comfrey root liquid extract was investigated for its ability to induce gene mutations in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with and without metabolic activation using the mammalian microsomal fraction S9 mix. Reference mutagens were used to check the validity of the experiments. Comfrey root fluid extract showed no biologically relevant increases in revertant colony numbers of any of the five tester strains, neither in the presence nor in the absence of metabolic activation. In conclusion, the comfrey root fluid extract contained in Kytta-Salbe® f and Kytta-Plasma® f was not mutagenic in the bacterial reverse mutation assay. Copyright © 2009 John Wiley & Sons, Ltd. [source] The Arabidopsis ATRIP ortholog is required for a programmed response to replication inhibitorsTHE PLANT JOURNAL, Issue 3 2009Paul R. Sweeney Summary The programmed response to replication inhibitors in eukaryotic cells requires the protein kinase ATR (ataxia telangiectasia mutated and rad3-related), which is activated primarily through the persistence of replication protein A (RPA)-bound single-stranded DNA at stalled replication forks and sites of DNA damage undergoing excision repair. Once activated, ATR initiates a cascade of events, including cell-cycle arrest and induction of DNA repair, to mitigate the mutagenic effects of DNA replication in the presence of damage and/or blockage. While many of the molecular regulators of ATR have been determined in yeast and animal cells, little is known about ATR regulation in plants. To genetically define ATR regulatory pathways in Arabidopsis, we describe here a genetic screen for identifying mutants that display a characteristic phenotype of Arabidopsis atr null mutants , hypersensitivity to the replication blocking agent hydroxyurea (HU). Employing this screen, we isolated a novel mutant, termed hus2 (hydroxyurea-sensitive), that displays hypersensitivity to HU, aphidicolin and ionizing radiation, similar to atr mutants. In addition, cell-cycle progression in response to replication blocks and ionizing radiation is defective in hus2, displaying a nearly identical phenotype to atr mutants. Positional cloning of hus2 reveals a gene sequence similar to yeast Rad26/Ddc2 and ATRIP (ATR interacting protein), suggesting that hus2 encodes an Arabidopsis ATRIP ortholog. [source] Chromophoric potential of the 4(3H)-quinazolinones: a reviewCOLORATION TECHNOLOGY, Issue 3 2004Harjinder Singh Bhatti The last few decades have seen significant developments in the use of heterocyclic compounds in dyestuff and pigment chemistry. The design of newer heterocyclic systems has been a major target area and has focused on economically viable synthesis, absence of effluent problems and freedom from carcinogenic and mutagenic effects. The present article reviews the chemical and patent literature on the chromophoric potential of the 4(3H)-quinazolinone ring system, including dyes, pigments, fluorescent brightening agents, luminescent inks, electroluminescent devices, photographic couplers, colour formers and photographic fog inhibitors. [source] | |||||||||||||