Database : MEDLINE
Search on : Leukemia and L5178 [Words]
References found : 872 [refine]
Displaying: 1 .. 10   in format [Detailed]

page 1 of 88 go to page                         

  1 / 872 MEDLINE  
              next record last record
select
to print
Photocopy
Full text

[PMID]: 27198565
[Au] Autor:Sannikova EP; Bulushova NV; Cheperegin SE; Gubaydullin II; Chestukhina GG; Ryabichenko VV; Zalunin IA; Kotlova EK; Konstantinova GE; Kubasova TS; Shtil AA; Pokrovsky VS; Yarotsky SV; Efremov BD; Kozlov DG
[Ad] Address:State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
[Ti] Title:The Modified Heparin-Binding L-Asparaginase of Wolinella succinogenes.
[So] Source:Mol Biotechnol;58(8-9):528-39, 2016 Sep.
[Is] ISSN:1559-0305
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The modified asparaginase Was79 was derived from the recombinant wild-type L-asparaginase of Wolinella succinogenes. The Was79 contains the amino acid substitutions V23Q and K24T responsible for the resistance to trypsinolysis and the N-terminal heparin-binding peptide KRKKKGKGLGKKR responsible for the binding to heparin and tumor K562 cells in vitro. When tested on a mouse model of Fischer lymphadenosis L5178Y, therapeutic efficacy of Was79 was significantly higher than that of reference enzymes at all single therapeutic doses used (125-8000 IU/kg). At Was79 single doses of 500-8000 IU/kg, the complete remission rate of 100 % was observed. The Was79 variant can be expressed intracellularly in E. coli as a less immunogenic formyl-methionine-free form at high per cell production levels.
[Mh] MeSH terms primary: Antineoplastic Agents/administration & dosage
Asparaginase/genetics
Asparaginase/metabolism
Heparin/metabolism
Leukemia L5178/drug therapy
Wolinella/enzymology
[Mh] MeSH terms secundary: Amino Acid Substitution
Animals
Antineoplastic Agents/pharmacology
Asparaginase/administration & dosage
Asparaginase/pharmacology
Bacterial Proteins/administration & dosage
Bacterial Proteins/genetics
Bacterial Proteins/metabolism
Bacterial Proteins/pharmacology
Cell Proliferation/drug effects
Cell Survival/drug effects
Humans
K562 Cells
Mice
Recombinant Proteins/metabolism
Recombinant Proteins/pharmacology
Wolinella/genetics
Xenograft Model Antitumor Assays
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Antineoplastic Agents); 0 (Bacterial Proteins); 0 (Recombinant Proteins); 9005-49-6 (Heparin); EC 3.5.1.1 (Asparaginase)
[Em] Entry month:1703
[Cu] Class update date: 171108
[Lr] Last revision date:171108
[Js] Journal subset:IM
[Da] Date of entry for processing:160521
[St] Status:MEDLINE
[do] DOI:10.1007/s12033-016-9950-1

  2 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 26046975
[Au] Autor:Maisanaba S; Prieto AI; Puerto M; Gutiérrez-Praena D; Demir E; Marcos R; Cameán AM
[Ad] Address:Area of Toxicology, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain.
[Ti] Title:In vitro genotoxicity testing of carvacrol and thymol using the micronucleus and mouse lymphoma assays.
[So] Source:Mutat Res Genet Toxicol Environ Mutagen;784-785:37-44, 2015 Jun.
[Is] ISSN:1879-3592
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Currently, antimicrobial additives derived from essential oils (Eos) extracted from plants or spices, such as Origanum vulgare, are used in food packaging. Thymol and carvacrol, the major EO compounds of O. vulgare, have demonstrated their potential use as active additives. These new applications use high concentrations, thereby increasing the concern regarding their toxicological profile and especially their genotoxic risk. The aim of this work was to investigate the potential in vitro genotoxicity of thymol (0-250 µM) and carvacrol (0-2500 µM) at equivalent doses to those used in food packaging. The micronucleus (MN) test and the mouse lymphoma (MLA) assay on L5178Y/Tk(±) mouse lymphoma cells were used. The negative results for thymol with the MN with and without the S9 fraction and also with the MLA assay reinforce the view that this compound is not genotoxic in mammalian cells. However, carvacrol presented slight genotoxic effects, but only in the MN test at the highest concentration assayed (700 µM) and in the absence of metabolic activation. The lack of genotoxic response in the MLA assay after 4 and 24h of exposure indicates a low genotoxic potential for carvacrol. Alternatively, the general negative findings observed in both assays suggest that the MN results of carvacrol are marginal data without biological relevance. These results can be useful to identify the appropriate concentrations of these substances to be used as additives in food packaging.
[Mh] MeSH terms primary: DNA, Neoplasm/drug effects
Food Additives/toxicity
Monoterpenes/toxicity
Thymol/toxicity
[Mh] MeSH terms secundary: Animals
Cell Line, Tumor
DNA Damage
Dose-Response Relationship, Drug
In Vitro Techniques
Leukemia L5178
Mice
Micronucleus Tests
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (DNA, Neoplasm); 0 (Food Additives); 0 (Monoterpenes); 3J50XA376E (Thymol); 9B1J4V995Q (carvacrol)
[Em] Entry month:1508
[Cu] Class update date: 150606
[Lr] Last revision date:150606
[Js] Journal subset:IM
[Da] Date of entry for processing:150606
[St] Status:MEDLINE

  3 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
PubMed Central Full text
Full text

[PMID]: 25701764
[Au] Autor:Codd EE; Ng HH; McFarlane C; Riccio ES; Doppalapudi R; Mirsalis JC; Horton RJ; Gonzalez AE; Garcia HH; Gilman RH; Cysticercosis Working Group in Peru
[Ad] Address:Codd Consulting, LLC, Blue Bell, PA, USA ellen.codd@verizon.net.
[Ti] Title:Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: toward first in human studies.
[So] Source:Int J Toxicol;34(2):129-37, 2015 Mar-Apr.
[Is] ISSN:1092-874X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases.
[Mh] MeSH terms primary: Anthelmintics/pharmacokinetics
Benzimidazoles/pharmacokinetics
[Mh] MeSH terms secundary: Administration, Oral
Animals
Anthelmintics/adverse effects
Anthelmintics/toxicity
Benzimidazoles/adverse effects
Benzimidazoles/toxicity
Cardiovascular System/drug effects
Dogs
Dose-Response Relationship, Drug
Female
Leukemia L5178/genetics
Male
Mice
Micronucleus Tests
Mutagenicity Tests
Rats
Rats, Sprague-Dawley
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Anthelmintics); 0 (Benzimidazoles); OMP2H17F9E (oxfendazole)
[Em] Entry month:1604
[Cu] Class update date: 170922
[Lr] Last revision date:170922
[Js] Journal subset:IM
[Da] Date of entry for processing:150222
[St] Status:MEDLINE
[do] DOI:10.1177/1091581815569582

  4 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25651039
[Au] Autor:Szumiel I
[Ad] Address:Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology , Warsaw , Poland.
[Ti] Title:From radioresistance to radiosensitivity: In vitro evolution of L5178Y lymphoma.
[So] Source:Int J Radiat Biol;91(6):465-71, 2015 Jun.
[Is] ISSN:1362-3095
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PURPOSE: To discuss the possible reasons for the loss of tumourigenicity and the acquisition of new phenotypic features (among them, sensitivity to X and UVC radiations) as a result of in vitro cultivation of L5178Y lymphoma cells. RESULTS: Ten years ago the phenotypic differences between LY-R (original L5178Y maintained in vivo and examined in vitro) and LY-S lines were reviewed in detail by the author. The loss of tumourigenicity of LY-R cells upon in vitro cultivation accompanying the acquirement of the LY-S phenotype had been described earlier by Beer et al. (1983). In spite of their common origin, the sublines were shown to differ in their relative sensitivity to a number of DNA damaging agents and in numerous other features. Here, selected differences between LY-R and LY-S lines are briefly reviewed. It is proposed that Wallace's concept (2010a) that mitochondria are the interface between environmental conditions and the genome may explain the LY-R-LY-S conversion under prolonged in vitro cultivation. CONCLUSION: The differences between the LY lines were probably of epigenetic rather than genetic character. The properties of LY-R cells changed as a result of exposure to an oxic in vitro milieu. The changes could be preconditioned by heteroplasmy and the selection of cells endowed with mitochondria best fitted to a high oxygen-low carbon dioxide environment.
[Mh] MeSH terms primary: Leukemia L5178/radiotherapy
Radiation Tolerance
[Mh] MeSH terms secundary: Animals
Biological Evolution
Cell Line, Tumor
Cell Proliferation
DNA Damage
Epigenesis, Genetic/radiation effects
Genomic Instability/radiation effects
Leukemia L5178/genetics
Leukemia L5178/pathology
Mice
Mitochondria/genetics
Mitochondria/radiation effects
Oxidative Stress/radiation effects
Phenotype
Radiation Tolerance/genetics
Tumor Microenvironment/genetics
Tumor Microenvironment/radiation effects
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Em] Entry month:1508
[Cu] Class update date: 150601
[Lr] Last revision date:150601
[Js] Journal subset:IM; S
[Da] Date of entry for processing:150205
[St] Status:MEDLINE
[do] DOI:10.3109/09553002.2014.996263

  5 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 23778052
[Au] Autor:Cheng TF; Patton GW; Muldoon-Jacobs K
[Ad] Address:US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety, Division of Food Contact Notification, College Park, MD 20740, USA.
[Ti] Title:Can the L5178Y Tk+/- mouse lymphoma assay detect epigenetic silencing?
[So] Source:Food Chem Toxicol;59:187-90, 2013 Sep.
[Is] ISSN:1873-6351
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The mouse lymphoma L5178Y Tk(+/-) assay is broadly used in toxicology to assess genotoxicity because of its known sensitivity to genotoxicants that act through a variety of mechanisms, which may include epigenetic DNA methylation. This brief article highlights the studies that have contributed to this conjecture and suggests an addition to the experimental design that could identify if the test substance is a potential epimutagen acting via hypermethylation.
[Mh] MeSH terms primary: Antimetabolites, Antineoplastic/metabolism
Epigenetic Repression/drug effects
Leukemia L5178/metabolism
Mutagenicity Tests
Mutagens/toxicity
Neoplasm Proteins/metabolism
Thymidine Kinase/metabolism
[Mh] MeSH terms secundary: Aminopterin/metabolism
Aminopterin/pharmacology
Animals
Antimetabolites, Antineoplastic/pharmacology
Cell Line, Tumor
Cell Survival/drug effects
Clone Cells
DNA Methylation/drug effects
Drug Resistance, Neoplasm/drug effects
Evaluation Studies as Topic
Hypoxanthine/metabolism
Leukemia L5178/drug therapy
Leukemia L5178/enzymology
Mice
Mutation/drug effects
Neoplasm Proteins/genetics
Thymidine/metabolism
Thymidine Kinase/genetics
Trifluridine/metabolism
Trifluridine/pharmacology
[Pt] Publication type:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Name of substance:0 (Antimetabolites, Antineoplastic); 0 (Mutagens); 0 (Neoplasm Proteins); 2TN51YD919 (Hypoxanthine); EC 2.7.1.21 (Thymidine Kinase); EC 2.7.1.21 (thymidine kinase 1); JYB41CTM2Q (Aminopterin); RMW9V5RW38 (Trifluridine); VC2W18DGKR (Thymidine)
[Em] Entry month:1403
[Cu] Class update date: 130819
[Lr] Last revision date:130819
[Js] Journal subset:IM
[Da] Date of entry for processing:130620
[St] Status:MEDLINE

  6 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 23767930
[Au] Autor:Åsgård R; Hellman B
[Ad] Address:Division of Toxicology, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
[Ti] Title:Effect of ß-carotene on catechol-induced genotoxicity in vitro: evidence of both enhanced and reduced DNA damage.
[So] Source:Free Radic Res;47(9):692-8, 2013 Sep.
[Is] ISSN:1029-2470
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Intake of antioxidants from the diet has been recognized to have beneficial health effects, but the potential benefit of taking antioxidants such as ß-carotene as supplements is controversial. The aim of the present study was to evaluate the potential protective effects of a physiologically relevant concentration (2 µM) of ß-carotene on the DNA damaging effects of catechol in mouse lymphoma L5178Y cells. Two different exposure protocols were used: simultaneous exposure to ß-carotene and catechol for 3 h; and exposure to catechol for 3 h after 18 h pre-treatment with the vitamin. DNA damage was evaluated using the comet assay (employing one procedure for general damage, and another procedure, which also included oxidative DNA damage). Independent of exposure protocol and procedure for comet assay, ß-carotene did not increase the basal level of DNA damage. However, at the highest concentration of catechol (1 mM), ß-carotene was found to clearly increase the level of catechol-induced DNA damage, especially in the pre-treated cells. Interestingly, an opposite effect was observed at lower concentrations of catechol, but the ß-carotene related reduction of catechol-induced genotoxicity was significant (P < 0.05) only for the procedure including oxidative damage induced by 0.5 mM catechol. Taken together our results indicate that ß- carotene can both reduce and enhance the DNA damaging effects of a genotoxic agent such as catechol. This indicates that it is the level of catechol-induced DNA damage that seems to determine whether ß-carotene should be regarded as a beneficial or detrimental agent when it comes to its use as a dietary supplement.
[Mh] MeSH terms primary: Antioxidants/pharmacology
DNA Damage/drug effects
Oxidative Stress
beta Carotene/pharmacology
[Mh] MeSH terms secundary: Animals
Catechols/pharmacology
Dietary Supplements
Humans
Leukemia L5178
Mice
Mutagenicity Tests
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Antioxidants); 0 (Catechols); 01YAE03M7J (beta Carotene); LF3AJ089DQ (catechol)
[Em] Entry month:1403
[Cu] Class update date: 130813
[Lr] Last revision date:130813
[Js] Journal subset:IM
[Da] Date of entry for processing:130618
[St] Status:MEDLINE
[do] DOI:10.3109/10715762.2013.815346

  7 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 23220485
[Au] Autor:Crooks I; Dillon DM; Scott JK; Ballantyne M; Meredith C
[Ad] Address:British American Tobacco, Group Research and Development, Regents Park Road, Southampton, Hampshire, SO15 8TL, United Kingdom. Ian_Crooks@bat.com
[Ti] Title:The effect of long term storage on tobacco smoke particulate matter in in vitro genotoxicity and cytotoxicity assays.
[So] Source:Regul Toxicol Pharmacol;65(2):196-200, 2013 Mar.
[Is] ISSN:1096-0295
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Particulate matter (PM) collected from mainstream tobacco smoke is a test article commonly used for in vitro genotoxicity and cytotoxicity testing of combustible tobacco products. However, little published data exists concerning the stability of PM. We completed a 2 year study to quantify the effect of PM storage at -80 °C, on the genotoxicity and cytotoxicity of PM generated from 3R4F and M4A reference cigarettes. The Ames test, Micronucleus assay (MNvit), Mouse Lymphoma assay (MLA) and the Neutral Red Uptake assay (NRU) were used. The majority of M4A and 3R4F PMs were genotoxic and cytotoxic at the timepoints tested. Some minor but statistically significant differences were observed for stored versus freshly prepared PM, but the magnitude of changes were within the variability observed for repeat testing.
[Mh] MeSH terms primary: Air Pollutants/toxicity
Mutagens/toxicity
Particulate Matter/toxicity
Smoke/adverse effects
Tobacco Smoke Pollution/adverse effects
[Mh] MeSH terms secundary: Air Pollutants/classification
Animals
BALB 3T3 Cells/drug effects
Cell Line
Cell Survival/drug effects
DNA/drug effects
DNA Damage
Drug Stability
Inhibitory Concentration 50
Leukemia L5178/drug therapy
Leukemia L5178/genetics
Mice
Mice, Inbred BALB C
Micronucleus Tests
Mutagens/classification
Neutral Red/metabolism
Particulate Matter/classification
Reproducibility of Results
Salmonella typhimurium/drug effects
Salmonella typhimurium/genetics
Time Factors
Tobacco
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Air Pollutants); 0 (Mutagens); 0 (Particulate Matter); 0 (Smoke); 0 (Tobacco Smoke Pollution); 261QK3SSBH (Neutral Red); 9007-49-2 (DNA)
[Em] Entry month:1307
[Cu] Class update date: 131121
[Lr] Last revision date:131121
[Js] Journal subset:IM
[Da] Date of entry for processing:121211
[St] Status:MEDLINE

  8 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy

[PMID]: 22753749
[Au] Autor:Danko B; Martins A; Chuang DW; Wang HC; Amaral L; Molnár J; Chang FR; Wu YC; Hunyadi A
[Ad] Address:Institute of Pharmacognosy, University of Szeged, Szeged, Hungary.
[Ti] Title:In vitro cytotoxic activity of novel protoflavone analogs - selectivity towards a multidrug resistant cancer cell line.
[So] Source:Anticancer Res;32(7):2863-9, 2012 Jul.
[Is] ISSN:1791-7530
[Cp] Country of publication:Greece
[La] Language:eng
[Ab] Abstract:BACKGROUND: Protoapigenone (PA), a natural flavonoid possessing an unusual p-quinol moiety on its B ring, is a prospective novel lead compound against cancer currently in development, together with WYC0209, a potent synthetic PA analog. Structure activity relationships (SAR) concerning different 1'-O-alkyl side-chains were also studied on two sets of derivatives. MATERIALS AND METHODS: Fifteen 1'-O-alkyl protoflavone derivatives were synthesized from genkwanin or 4'-hydroxy-6-methylflavone, thirteen of which are new compounds. All compounds were tested for their cytotoxic effect on four human cancer cell lines, such as HepG2 and Hep3B (hepatic), A549 (lung) and MDA-MB-231 (breast) cell lines, with doxorubicin as a positive control. All compounds, as well as PA, WYC0209 and fourteen of their previously reported analogs were also tested on a multidrug-resistant (MDR) sub-cell line of L5178 mouse T-cell lymphoma and on its parental counterpart (PAR). RESULTS: In general, derivatives bearing a free hydroxyl group at C-1' exerted the strongest activities, while C-1'-substituted compounds were found to be much weaker. Derivatives of 6-methylflavone exhibited mild, but statistically significant selectivity towards the MDR cell line. CONCLUSION: The results are in agreement with our previous findings for fundamental SAR of protoflavones. 6-Methylated protoflavones may serve as valuable leads for developing selective compounds against MDR cancer. Identical activity of other derivatives on the PAR and MDR cell lines suggests that cancer cells cannot exhibit resistance to protoflavones by ABCB1 efflux pump overexpression.
[Mh] MeSH terms primary: Antineoplastic Agents/pharmacology
Flavones/pharmacology
[Mh] MeSH terms secundary: Animals
Antineoplastic Agents/chemistry
Cell Line, Tumor
Cell Survival/drug effects
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Flavones/chemistry
Hep G2 Cells
Humans
Leukemia L5178/drug therapy
Mice
Structure-Activity Relationship
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Antineoplastic Agents); 0 (Flavones)
[Em] Entry month:1210
[Cu] Class update date: 120703
[Lr] Last revision date:120703
[Js] Journal subset:IM
[Da] Date of entry for processing:120704
[St] Status:MEDLINE

  9 / 872 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy

[PMID]: 22739010
[Au] Autor:Kawanishi M; Okuyama K; Shiraishi K; Matsuda Y; Taniguchi R; Shiomi N; Yonezawa M; Yagi T
[Ad] Address:Radiation Research Center and Graduate School of Science, Osaka Prefecture University, Osaka, Japan.
[Ti] Title:Growth retardation of Paramecium and mouse cells by shielding them from background radiation.
[So] Source:J Radiat Res;53(3):404-10, 2012.
[Is] ISSN:1349-9157
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:In the 1970s and 1980s, Planel et al. reported that the growth of paramecia was decreased by shielding them from background radiation. In the 1990s, Takizawa et al. found that mouse cells displayed a decreased growth rate under shielded conditions. The purpose of the present study was to confirm that growth is impaired in organisms that have been shielded from background radiation. Radioprotection was produced with a shielding chamber surrounded by a 15 cm thick iron wall and a 10 cm thick paraffin wall that reduced the γ ray and neutron levels in the chamber to 2% and 25% of the background levels, respectively. Although the growth of Paramecium tetraurelia was not impaired by short-term radioprotection (around 10 days), which disagreed with the findings of Planel et al., decreased growth was observed after long-term (40-50 days) radiation shielding. When mouse lymphoma L5178Y cells were incubated inside or outside of the shielding chamber for 7 days, the number of cells present on the 6th and 7th days under the shielding conditions was significantly lower than that present under the non-shielding conditions. These inhibitory effects on cell growth were abrogated by the addition of a ¹³7Cs γ-ray source disk to the chamber. Furthermore, no growth retardation was observed in XRCC4-deficient mouse M10 cells, which display impaired DNA double strand break repair.
[Mh] MeSH terms primary: Background Radiation/adverse effects
Cell Proliferation/radiation effects
Paramecium tetraurelia/growth & development
Paramecium tetraurelia/radiation effects
[Mh] MeSH terms secundary: Animals
Cell Line, Tumor
DNA Repair
Leukemia L5178
Mice
Radiation Protection
Time Factors
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1301
[Cu] Class update date: 120628
[Lr] Last revision date:120628
[Js] Journal subset:IM
[Da] Date of entry for processing:120629
[St] Status:MEDLINE

  10 / 872 MEDLINE  
              first record previous record
select
to print
Photocopy
Full text

[PMID]: 22564015
[Au] Autor:Geter DR; Zhang F; Schisler MR; Wood AJ; Kan HL; Jeong YC; Bartels MJ; McFadden L; Gollapudi BB
[Ad] Address:Toxicology and Environmental Research & Consulting, The Dow Chemical Company, Midland, Michigan, USA.
[Ti] Title:Genetic damage, but limited evidence of oxidative stress markers in diethyl maleate-induced glutathione depleted mouse lymphoma L5178Y (TK(+/-)) cell cultures.
[So] Source:Toxicol Mech Methods;22(7):547-54, 2012 Sep.
[Is] ISSN:1537-6524
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Depletion of glutathione (GSH) in cells exposed to certain xenobiotics has been proposed to result in oxidative stress, which could lead to damage of cellular macromolecules such as proteins, lipids, and DNA. Diethyl maleate (DEM) is known to conjugate with GSH and rapidly lower cellular GSH levels. The objective of this study was to investigate the influence of DEM-induced GSH depletion on various genotoxicity and gene expression end points in mouse lymphoma L5178Y (TK(+/-)) cell cultures. Cells were exposed to DEM for 4 h at concentrations of 0, 6.7, 13.5, 26.9, 53.8, 107.6, 215.3, and 430.6 µg/mL (0.039-2.5 mM). Genotoxicity was evaluated by examining the induction of in vitro micronuclei (20 h post-treatment) and DNA strand breaks as measured by comet (immediately following treatment), and correlating these observations to cellular GSH levels. In the current study, GSH was decreased more than 50% at the lowest test concentration (6.7 µg/mL) and more than 95% at ≥ 107.6 µg/mL. A significant increase in micronuclei and DNA strand breaks was observed at concentrations of ≥ 26.9 µg/mL. Gene expression of seven apoptosis and oxidative-stress related genes showed significant alterations in only three genes only at the highest test concentration. Quantifiable levels of 8-OH-dG (≥ 2 adducts per 1 × 10(8) NT) were not detected at any treatment concentration. These results demonstrate an association between DEM-induced genotoxicity and GSH depletion in mouse lymphoma L5178Y (TK(+/-)) cells, but not with other oxidative markers.
[Mh] MeSH terms primary: DNA Damage
Glutathione/metabolism
Maleates/toxicity
Micronuclei, Chromosome-Defective/chemically induced
Mutagens/toxicity
Oxidative Stress/drug effects
[Mh] MeSH terms secundary: Animals
Apoptosis/drug effects
Apoptosis/genetics
Biomarkers/metabolism
Cell Line, Tumor
Cell Survival/drug effects
Comet Assay
DNA Adducts/metabolism
Deoxyguanosine/analogs & derivatives
Deoxyguanosine/metabolism
Dose-Response Relationship, Drug
Gene Expression/drug effects
Leukemia L5178/pathology
Mice
Micronucleus Tests
Oxidative Stress/genetics
Reactive Oxygen Species/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Biomarkers); 0 (DNA Adducts); 0 (Maleates); 0 (Mutagens); 0 (Reactive Oxygen Species); 88847-89-6 (8-oxo-7-hydrodeoxyguanosine); G81WQB56OL (diethyl maleate); G9481N71RO (Deoxyguanosine); GAN16C9B8O (Glutathione)
[Em] Entry month:1301
[Cu] Class update date: 171116
[Lr] Last revision date:171116
[Js] Journal subset:IM
[Da] Date of entry for processing:120509
[St] Status:MEDLINE
[do] DOI:10.3109/15376516.2012.692111


page 1 of 88 go to page                         
   


Refine the search
  Database : MEDLINE Advanced form   

    Search in field  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/PAHO/WHO - Latin American and Caribbean Center on Health Sciences Information