Search results for: Azeddine Elhajouji

Items from 1 to 20 out of 22 results

article

Intra‐ and inter‐laboratory reproducibility of the rat blood Pig‐a gene mutation assay

Stephen D. Dertinger, Svetlana L. Avlasevich, Dorothea K. Torous, Jeffrey C. Bemis, more

Environmental and Molecular Mutagenesis > 61 > 5 > 500 - 507

The in vivo Pig‐a assay is being used in safety studies to evaluate the potential of chemicals to induce somatic cell gene mutations. Ongoing work is aimed at developing an Organization for Economic Cooperation and Development (OECD) test guideline to support routine use for regulatory purposes (OECD project number 4.93). Among the requirements for OECD approval are demonstrations of assay reliability,...

article

Application of the adverse outcome pathway framework to genotoxic modes of action

Jennifer C. Sasaki, Ashley Allemang, Steven M. Bryce, Laura Custer, more

Environmental and Molecular Mutagenesis > 61 > 1 > 114 - 134

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity...

article

Analysis of negative historical control group data from the in vitro micronucleus assay using TK6 cells

David P. Lovell, Mick Fellows, Francesco Marchetti, Joan Christiansen, more

Mutation Research/Genetic Toxicology and Environmental Mutagenesis > 2018 > 825 > C > 40-50

The recent revisions of the Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines emphasize the importance of historical negative controls both for data quality and interpretation. The goal of a HESI Genetic Toxicology Technical Committee (GTTC) workgroup was to collect data from participating laboratories and to conduct a statistical analysis to understand...

article

HUMN project initiative and review of validation, quality control and prospects for further development of automated micronucleus assays using image cytometry systems

Michael Fenech, Micheline Kirsch-Volders, Andrea Rossnerova, Radim Sram, more

International Journal of Hygiene and Environmental Health > 2013 > 216 > 5 > 541-552

The use of micronucleus (MN) assays in in vitro genetic toxicology testing, radiation biodosimetry and population biomonitoring to study the genotoxic impacts of environment gene-interactions has steadily increased over the past two decades. As a consequence there has been a strong interest in developing automated systems to score micronuclei, a biomarker of chromosome breakage or loss, in mammalian...

article

Flow cytometric 96‐well microplate‐based in vitro micronucleus assay with human TK6 cells: Protocol optimization and transferability assessment

Steven M. Bryce, Svetlana L. Avlasevich, Jeffrey C. Bemis, Matthew Tate, more

Environmental and Molecular Mutagenesis > 54 > 3 > 180 - 194

An automated approach for scoring in vitro micronuclei (MN) has been described in which flow cytometric analysis is combined with compound exposure, processing, and sampling in a single 96‐well plate (Bryce SM et al. [2010]: Mutat Res 703:191‐199). The current report describes protocol optimization and an interlaboratory assessment of the assay's transferability and reproducibility. In a training...

article

Miniaturized flow cytometry‐based in vitro primary human lymphocyte micronucleus assay—validation study

Magdalena Lukamowicz‐Rajska, Micheline Kirsch‐Volders, Willi Suter, Hansjoerg Martus, more

Environmental and Molecular Mutagenesis > 53 > 4 > 260 - 270

Most in vitro mammalian genotoxicity assays show a low specificity (high rate of irrelevant positive results), and therefore, lead to an increase in follow‐up in vivo genotoxicity testing. One of the sources of the high rate of in vitro irrelevant positive results that find no confirmation in in vivo studies may be the characteristics of the test system used. It has been shown that cells that are...

article

International Pig‐a gene mutation assay trial: Evaluation of transferability across 14 laboratories

Stephen D. Dertinger, Souk Phonethepswath, Pamela Weller, John Nicolette, more

Environmental and Molecular Mutagenesis > 52 > 9 > 690 - 698

A collaborative international trial was conducted to evaluate the reproducibility and transferability of an in vivo mutation assay based on the enumeration of CD59‐negative rat erythrocytes, a phenotype that is indicative of Pig‐a gene mutation. Fourteen laboratories participated in this study, where anti‐CD59‐PE, SYTO 13 dye, and flow cytometry were used to determine the frequency of CD59‐negative...

article

In vitro genotoxicity test approaches with better predictivity: Summary of an IWGT workshop

Stefan Pfuhler, Mick Fellows, Jan van Benthem, Raffaella Corvi, more

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2011 > 723 > 2 > 101-107

Improving current in vitro genotoxicity tests is an ongoing task for genetic toxicologists. Further, the question on how to deal with positive in vitro results that are demonstrated to not predict genotoxicity or carcinogenicity potential in rodents or humans is a challenge. These two aspects were addressed at the 5th International Workshop on Genotoxicity Testing (IWGT) held in Basel, Switzerland,...

article

A flow cytometry based in vitro micronucleus assay in TK6 cells—Validation using early stage pharmaceutical development compounds

Magdalena Lukamowicz, Katherine Woodward, Micheline Kirsch‐Volders, Willi Suter, more

Environmental and Molecular Mutagenesis > 52 > 5 > 363 - 372

The micronucleus test (MNT) is a well established test for detecting clastogenic and aneugenic compounds. Despite the assay's advantages, the MNT may produce false positive and false negative results in some conditions. This fact may be related to the underestimation of apoptosis or necrosis, the p53 status of the cell system or the cytotoxicity assay, and the top dose selection. The purpose of our...

article

The in vitro MN assay in 2011: origin and fate, biological significance, protocols, high throughput methodologies and toxicological relevance

Micheline Kirsch-Volders, Gina Plas, Azeddine Elhajouji, Magdalena Lukamowicz, more

Archives of Toxicology > 2011 > 85 > 8 > 873-899

Micronuclei (MN) are small, extranuclear bodies that arise in dividing cells from acentric chromosome/chromatid fragments or whole chromosomes/chromatids lagging behind in anaphase and are not included in the daughter nuclei at telophase. The mechanisms of MN formation are well understood; their possible postmitotic fate is less evident. The MN assay allows detection of both aneugens and clastogens,...

article

Mitomycin C, 5-fluoruracil, colchicine and etoposide tested in the in vitro mammalian cell micronucleus test (MNvit) in the human lymphoblastoid cell line TK6 at Novartis in support of OECD draft Test Guideline 487

Azeddine Elhajouji

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2010 > 702 > 2 > 157-162

The following reference genotoxic agents were tested in the in vitro micronucleus test, at Novartis, Basel, Switzerland. Mitomycin C, 5-fluoruracil, colchicine and etoposide were tested in the human lymphoblastoid cell line TK6, with and without cytokinesis block (in the presence of cytochalasin B). This was done in support of the toxicity measures recommended in the draft OECD Test Guideline on In...

article

Flow cytometry peripheral blood micronucleus test in vivo: Determination of potential thresholds for aneuploidy induced by spindle poisons

Zoryana Cammerer, Martin M. Schumacher, Micheline Kirsch‐Volders, Willi Suter, more

Environmental and Molecular Mutagenesis > 51 > 4 > 278 - 284

Non‐DNA binding genotoxins (e.g., aneugens), unlike DNA‐binding genotoxins, are theoretically expected to show thresholded concentration‐effect response curves. This is a major issue in genetic toxicology testing because the identification of thresholds in vivo can provide a safety margin for exposure to a particular compound. In the current study we measured micronucleus induction by flow cytometry...

article

Reduction of use of animals in regulatory genotoxicity testing: Identification and implementation opportunities—Report from an ECVAM workshop

Stefan Pfuhler, David Kirkland, Peter Kasper, Makoto Hayashi, more

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2009 > 680 > 1-2 > 31-42

In vivo genetic toxicology tests measure direct DNA damage or the formation of gene or chromosomal mutations, and are used to predict the mutagenic and carcinogenic potential of compounds for regulatory purposes and/or to follow-up positive results from in vitro testing. These tests are widely used and consume large numbers of animals, with a foreseeable marked increase as a result of the EU chemicals...

article

Inhalation of formaldehyde does not induce systemic genotoxic effects in rats

Günter Speit, Jasmin Zeller, Oliver Schmid, Azeddine Elhajouji, more

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2009 > 677 > 1-2 > 76-85

Male Fischer-344 rats were exposed to formaldehyde (FA) by inhalation for 4 weeks (6h/day, 5 days/week). Groups of six rats each were exposed to the target concentrations of 0, 0.5, 1, 2, 6, 10 and 15ppm. Potential systemic genotoxic effects were investigated as part of a comprehensive study on local and systemic toxic and genotoxic effects. For this purpose, peripheral blood samples were obtained...

article

Interlaboratory evaluation of a flow cytometric, high content in vitro micronucleus assay

Steven M. Bryce, Svetlana L. Avlasevich, Jeffrey C. Bemis, Magdalena Lukamowicz, more

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2008 > 650 > 2 > 181-195

An international, multi-lab trial was conducted to evaluate a flow cytometry-based method for scoring micronuclei in mouse lymphoma L5178Y cells [S.L. Avlasevich, S.M. Bryce, S.E. Cairns, S.D. Dertinger, In vitro micronucleus scoring by flow cytometry: differential staining of micronuclei versus apoptotic and necrotic chromatin enhances assay reliability, Environ. Mol. Mutagen. 47 (2006) 56–66]. A...

article

How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: Report of an ECVAM Workshop

David Kirkland, Stefan Pfuhler, David Tweats, Marilyn Aardema, more

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2007 > 628 > 1 > 31-55

Workshop participants agreed that genotoxicity tests in mammalian cells in vitro produce a remarkably high and unacceptable occurrence of irrelevant positive results (e.g. when compared with rodent carcinogenicity). As reported in several recent reviews, the rate of irrelevant positives (i.e. low specificity) for some studies using in vitro methods (when compared to this “gold standard”) means that...

article

In vivo micronucleus test with flow cytometry after acute and chronic exposures of rats to chemicals

Zoryana Cammerer, Azeddine Elhajouji, Willi Suter

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2007 > 626 > 1-2 > 26-33

The use of flow cytometry with rat peripheral blood erythrocytes is expected to increase the sensitivity of the in vivo micronucleus test and allows assessment of the genotoxic effects at doses that may be equal or close to those relevant to human exposure. However, there was a limitation to the use of rat peripheral blood erythrocytes since the spleen selectively removes micronucleated erythrocytes...

article

Methylphenidate is not clastogenic in cultured human lymphocytes and in the mouse bone-marrow micronucleus test

Willi Suter, Hans-Joerg Martus, Azeddine Elhajouji

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2006 > 607 > 2 > 153-159

Methylphenidate (MPH) is one of the most frequently prescribed drugs for the treatment of attention deficit hyperactivity disorder (ADHD). A report on cytogenetic effects observed in peripheral lymphocytes from children treated for 3 months with MPH raised questions about the genetic toxicity of this compound. A critical review of this data concluded that the cytogenetic effects in treated children...

article

V. Using L5178Y cells

Jo Oliver, Jean-Roch Meunier, Takumi Awogi, Azeddine Elhajouji, more

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2006 > 607 > 1 > 125-152

In this report, results are presented from an international study of the in vitro micronucleus assay using mouse lymphoma L5178Y cells. This study was coordinated by an organizing committee supported by the SFTG (the French branch of the European Environmental Mutagen Society). Test chemicals included mannitol, bleomycin, 5-fluorouracil, colchicine and griseofulvin. Mitomycin C was used as a positive...

article

Concepts of threshold in mutagenesis and carcinogenesis

Micheline Kirsch-Volders, Marilyn Aardema, Azeddine Elhajouji

Mutation Research - Genetic Toxicology and Environmental Mutagenesis > 2000 > 464 > 1 > 3-11

Although the existence of a threshold in the dose effect relationship is well documented for many, if not most, types of toxicological effects the existence of a threshold for the mutagenic effects of ionising radiation and of certain chemicals has been questioned since the middle of the century and only recently the question of thresholds for radiation and chemical carcinogenesis has been addressed...

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Keywords

FLOW CYTOMETRY (8)
GENOTOXICITY (6)
MICRONUCLEUS TEST (5)
AUTOMATION (4)
MICRONUCLEI (4)
CYTOTOXICITY (3)
TK6 CELLS (3)
IN VITRO MICRONUCLEUS ASSAY (2)
MICRONUCLEUS (2)
MUTATION (2)
RETICULOCYTES (2)
ADVERSE OUTCOME PATHWAY (1)
ANEUGEN (1)
ANEUGENS (1)
ANIMAL TESTS (1)
ANIMAL USE (1)
APOPTOSIS (1)
CARCINOGENESIS (1)
CELL CYCLE (1)
CHECKPOINT (1)
CHROMOSOME ABERRATIONS (1)
CLASTOGEN (1)
CLASTOGENICITY (1)
COMET ASSAY (1)
CYTOCHALASIN B (1)
CYTOGENETIC EFFECTS (1)
CYTOKINESIS-BLOCK (1)
CYTOKINESIS-BLOCK MICRONUCLEUS ASSAY (1)
DNA–PROTEIN CROSS-LINKS (1)
FALSE POSITIVES (1)
GENOTOXIC COMPOUNDS (1)
GENOTOXICITY IN VITRO (1)
GENOTOXICITY IN VIVO (1)
HAZARD ASSESSMENT (1)
HISTORICAL NEGATIVE CONTROL DATA (1)
HUMAN LYMPHOCYTES (1)
IMAGE CYTOMETRY (1)
IN VITRO GENOTOXICITY TESTING (1)
IN VIVO (1)
INTERLABORATORY TRIAL (1)
L5178Y (1)
L5178Y CELLS (1)
LYMPHOCYTES (1)
METHYLPHENIDATE (1)
MINIATURIZATION (1)
MISLEADING POSITIVE RESULTS (1)
MITOTIC SPINDLE INHIBITORS (1)
MN‐RETS (1)
MODE OF ACTION (1)
MOUSE LYMPHOMA CELLS (1)
MPH (1)
MUTAGENESIS (1)
OECD TEST GUIDELINE 487 (1)
P53 (1)
PERIPHERAL BLOOD (1)
PIG‐A (1)
PIG‐A GENE (1)
POLYCHROMATIC ERYTHROCYTES (1)
POLYPLOIDY (1)
PREDICTIVE CAPACITY (1)
PROLIFERATION (1)
QUALITY CONTROL STATISTICS (1)
RAT PERIPHERAL BLOOD (1)
REDUCTION (1)
REDUCTION ANIMAL USE (1)
REPRODUCIBILITY (1)
RITALIN (1)
SAFETY ASSESSMENT (1)
SCREENING (1)
SISTER CHROMATID EXCHANGE TEST (1)
STATISTICAL MODELING (1)
THRESHOLD (1)
THRESHOLDS (1)
TK6 CELL LINE (1)
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Elsevier (14)
Wiley (7)
Springer (1)

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Search results for: Azeddine Elhajouji

Intra‐ and inter‐laboratory reproducibility of the rat blood Pig‐a gene mutation assay

Application of the adverse outcome pathway framework to genotoxic modes of action

Analysis of negative historical control group data from the in vitro micronucleus assay using TK6 cells

HUMN project initiative and review of validation, quality control and prospects for further development of automated micronucleus assays using image cytometry systems

Flow cytometric 96‐well microplate‐based in vitro micronucleus assay with human TK6 cells: Protocol optimization and transferability assessment

Miniaturized flow cytometry‐based in vitro primary human lymphocyte micronucleus assay—validation study

International Pig‐a gene mutation assay trial: Evaluation of transferability across 14 laboratories

In vitro genotoxicity test approaches with better predictivity: Summary of an IWGT workshop

A flow cytometry based in vitro micronucleus assay in TK6 cells—Validation using early stage pharmaceutical development compounds

The in vitro MN assay in 2011: origin and fate, biological significance, protocols, high throughput methodologies and toxicological relevance

Mitomycin C, 5-fluoruracil, colchicine and etoposide tested in the in vitro mammalian cell micronucleus test (MNvit) in the human lymphoblastoid cell line TK6 at Novartis in support of OECD draft Test Guideline 487

Flow cytometry peripheral blood micronucleus test in vivo: Determination of potential thresholds for aneuploidy induced by spindle poisons

Reduction of use of animals in regulatory genotoxicity testing: Identification and implementation opportunities—Report from an ECVAM workshop

Inhalation of formaldehyde does not induce systemic genotoxic effects in rats

Interlaboratory evaluation of a flow cytometric, high content in vitro micronucleus assay

How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: Report of an ECVAM Workshop

In vivo micronucleus test with flow cytometry after acute and chronic exposures of rats to chemicals

Methylphenidate is not clastogenic in cultured human lymphocytes and in the mouse bone-marrow micronucleus test

V. Using L5178Y cells

Concepts of threshold in mutagenesis and carcinogenesis

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