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Beate Miller - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the In Vitro micronucleus test as an alternative to the In Vitro chromosomal aberration assay : position of the GUM workIng group on the In Vitro micronucleus test
Mutation research, 1998Co-Authors: Beate Miller, Franziska Pötter-locher, Angelika Seelbach, Helga Stopper, Dietmar Utesch, Stephan MadleAbstract:In order to license a pharmaceutical or chemical, a compound has to be tested for several genotoxicity endpoInts, IncludIng the Induction of chromosomal aberrations In Vitro. A workIng group withIn the GUM has evaluated published data on the In Vitro micronucleus test with the aim of judgIng its suitability as a replacement for the In Vitro chromosomal aberration test. After strict rejection criteria were applied, a database IncludIng 96 publications and 34 compounds was obtaIned. For 30 of these compounds, data on both tests were available. For 24 of the 30, concordant results In both test systems were obtaIned (80% correlation). The discordant results In 6 compounds can be explaIned by a known or suspected aneugenic potential of these compounds. ConsiderIng that cell types and test protocols were extremely heterogeneous, this correlation is rather encouragIng. Comparison of the different protocols, and experience established withIn the workIng group yielded several recommendations for the routIne use of the In Vitro micronucleus test. Although many cell lInes are suitable, those most often used In genotoxicity testIng (e.g. CHL, CHO, V79, human lymphocytes, L5178Y mouse lymphoma cells) are recommended. CytochalasIn B may be used In the case of human lymphocytes; however, the possibility of its Interaction with aneugenic test compounds should be considered. For contInuously dividIng cell lInes, cytochalasIn B is not recommended by the workIng group. Although, there seems to be flexibility In the choice of treatment and samplIng times, the average generation time of the chosen cell lIne of choice should be taken Into account when determInIng samplIng time, and treatment of cells for at least one cell cycle duration is recommended. The use of appropriate cytotoxicity tests is strongly recommended. Although studies on some parameters of the test protocol may be useful, the Introduction of the In Vitro micronucleus test Into genotoxicity testIng and guidelInes should not be delayed. Even In its present state, the In Vitro micronucleus is a reliable genotoxicity test. Compared with the chromosomal aberration test, it detects aneugens more reliably, it is faster and easier to perform, and it has more statistical power and the possibility of automation.
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comparative evaluation of the In Vitro micronucleus test and the In Vitro chromosome aberration test Industrial experience
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 1997Co-Authors: Beate Miller, Franziska Locher, Veronique Thybaud, Silvio Albertini, Elisabeth LorgeAbstract:Abstract Because of its rapidness, simplicity and potential for automation, the measurement of micronucleated cells In vivo is not only equivalent to the analysis of chromosome aberrations, but often even preferred withIn routIne genotoxicity testIng. In order to evaluate the correlation between the In Vitro micronucleus assay (MNT) and the In Vitro chromosome aberration test (CA), we collected data from four pharmaceutical companies obtaIned either In ChInese hamster cell lInes (CHO-K5, CHO-K1, V79) or In human peripheral blood lymphocytes. Among the 57 compounds Included In this comparison, 45 compounds gave rise to concordant results In both assays (26 compounds negative In both assays; 19 compounds positive In both assays). The high percentage of concordance, i.e. about 79% is very promisIng and can be even Increased to about 88% by omittIng the 3 aneugenic compounds and 2 compounds InducIng endoreduplicated chromosomes which were found positive only In the In Vitro MNT. The results are remarkable In particular considerIng that most of the compounds evaluated are `standard' pharmaceutical compounds and thus are at most weak Inducers of chromosome damage. Our comparison strongly supports that the In Vitro micronucleus test is a suitable alternative to the In Vitro chromosome aberration assay. Moreover, the MNT has the potential of not only detectIng clastogens but additionally aneuploidy InducIng chemicals.
Julian D Mcclements - One of the best experts on this subject based on the ideXlab platform.
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In Vitro human digestion models for food applications
Food Chemistry, 2011Co-Authors: Sun Jin Hur, Beong Ou Lim, Eric A Decker, Julian D McclementsAbstract:Abstract In Vitro digestion models are widely used to study the structural changes, digestibility, and release of food components under simulated gastroIntestInal conditions. However, the results of In Vitro digestion models are often different to those found usIng In vivo models because of the difficulties In accurately simulatIng the highly complex physicochemical and physiological events occurrIng In animal and human digestive tracts. This paper provides an overview of current trends In the development and utilisation of In Vitro digestion models for foods, as well as Information that can be used to develop improved digestion models. Our survey of In Vitro digestion models found that the most predomInant food samples tested were plants, meats, fish, dairy, and emulsion-based foods. The most frequently used biological molecules Included In the digestion models were digestive enzymes (pancreatIn, pepsIn, trypsIn, chymotrypsIn, peptidase, α-amylase, and lipase), bile salts, and mucIn. In all the In Vitro digestion models surveyed, the digestion temperature was 37 °C although varyIng types and concentrations of enzymes were utilised. With regard to digestion times, 2 h (the stomach, small IntestIne, and large IntestIne each) was predomInantly employed. This survey enhances the understandIng of In Vitro digestion models and provides Indications for the development of improved In Vitro digestion models for foods or pharmaceuticals.
Stephan Madle - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the In Vitro micronucleus test as an alternative to the In Vitro chromosomal aberration assay : position of the GUM workIng group on the In Vitro micronucleus test
Mutation research, 1998Co-Authors: Beate Miller, Franziska Pötter-locher, Angelika Seelbach, Helga Stopper, Dietmar Utesch, Stephan MadleAbstract:In order to license a pharmaceutical or chemical, a compound has to be tested for several genotoxicity endpoInts, IncludIng the Induction of chromosomal aberrations In Vitro. A workIng group withIn the GUM has evaluated published data on the In Vitro micronucleus test with the aim of judgIng its suitability as a replacement for the In Vitro chromosomal aberration test. After strict rejection criteria were applied, a database IncludIng 96 publications and 34 compounds was obtaIned. For 30 of these compounds, data on both tests were available. For 24 of the 30, concordant results In both test systems were obtaIned (80% correlation). The discordant results In 6 compounds can be explaIned by a known or suspected aneugenic potential of these compounds. ConsiderIng that cell types and test protocols were extremely heterogeneous, this correlation is rather encouragIng. Comparison of the different protocols, and experience established withIn the workIng group yielded several recommendations for the routIne use of the In Vitro micronucleus test. Although many cell lInes are suitable, those most often used In genotoxicity testIng (e.g. CHL, CHO, V79, human lymphocytes, L5178Y mouse lymphoma cells) are recommended. CytochalasIn B may be used In the case of human lymphocytes; however, the possibility of its Interaction with aneugenic test compounds should be considered. For contInuously dividIng cell lInes, cytochalasIn B is not recommended by the workIng group. Although, there seems to be flexibility In the choice of treatment and samplIng times, the average generation time of the chosen cell lIne of choice should be taken Into account when determInIng samplIng time, and treatment of cells for at least one cell cycle duration is recommended. The use of appropriate cytotoxicity tests is strongly recommended. Although studies on some parameters of the test protocol may be useful, the Introduction of the In Vitro micronucleus test Into genotoxicity testIng and guidelInes should not be delayed. Even In its present state, the In Vitro micronucleus is a reliable genotoxicity test. Compared with the chromosomal aberration test, it detects aneugens more reliably, it is faster and easier to perform, and it has more statistical power and the possibility of automation.
Elisabeth Lorge - One of the best experts on this subject based on the ideXlab platform.
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comparative evaluation of the In Vitro micronucleus test and the In Vitro chromosome aberration test Industrial experience
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 1997Co-Authors: Beate Miller, Franziska Locher, Veronique Thybaud, Silvio Albertini, Elisabeth LorgeAbstract:Abstract Because of its rapidness, simplicity and potential for automation, the measurement of micronucleated cells In vivo is not only equivalent to the analysis of chromosome aberrations, but often even preferred withIn routIne genotoxicity testIng. In order to evaluate the correlation between the In Vitro micronucleus assay (MNT) and the In Vitro chromosome aberration test (CA), we collected data from four pharmaceutical companies obtaIned either In ChInese hamster cell lInes (CHO-K5, CHO-K1, V79) or In human peripheral blood lymphocytes. Among the 57 compounds Included In this comparison, 45 compounds gave rise to concordant results In both assays (26 compounds negative In both assays; 19 compounds positive In both assays). The high percentage of concordance, i.e. about 79% is very promisIng and can be even Increased to about 88% by omittIng the 3 aneugenic compounds and 2 compounds InducIng endoreduplicated chromosomes which were found positive only In the In Vitro MNT. The results are remarkable In particular considerIng that most of the compounds evaluated are `standard' pharmaceutical compounds and thus are at most weak Inducers of chromosome damage. Our comparison strongly supports that the In Vitro micronucleus test is a suitable alternative to the In Vitro chromosome aberration assay. Moreover, the MNT has the potential of not only detectIng clastogens but additionally aneuploidy InducIng chemicals.
Thomas Hartung - One of the best experts on this subject based on the ideXlab platform.
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good cell culture practices In Vitro toxicology
Toxicology in Vitro, 2017Co-Authors: Chantra Eskes, Ann Charlotte Boström, Gerhard Bowe, David Pamies, Giel Hendriks, Sandra Coecke, Amelie Piton, Thomas Hartung, Costanza RovidaAbstract:Abstract Good Cell Culture Practices (GCCP) is of high relevance to In Vitro toxicology. The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives for Animal TestIng (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP) joIned forces to address by means of an ESTIV 2016 pre-congress session the different aspects and applications of GCCP. The covered aspects comprised the current status of the OECD guidance document on Good In Vitro Method Practices, the importance of quality assurance for new technological advances In In Vitro toxicology IncludIng stem cells, and the optimized implementation of Good ManufacturIng Practices and Good Laboratory Practices for regulatory testIng purposes. General discussions raised the duality related to the difficulties In implementIng GCCP In an academic Innovative research framework on one hand, and on the other hand, the need for such GCCP prInciples In order to ensure reproducibility and robustness of In Vitro test methods for toxicity testIng. Indeed, if good cell culture prInciples are critical to take Into consideration for all uses of In Vitro test methods for toxicity testIng, the level of application of such prInciples may depend on the stage of development of the test method as well as on the applications of the test methods, i.e. , academic Innovative research vs. regulatory standardized test method.
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ecvam retrospective validation of In Vitro micronucleus test mnt
Mutagenesis, 2008Co-Authors: Raffaella Corvi, Thomas Hartung, Silvio Albertini, Sebastian Hoffmann, Daniela Maurici, Stefan Pfuhler, Jan Van Benthem, Philippe VanparysAbstract:In the past decade several studies comparIng the In Vitro chromosome aberration test (CAT) and the In Vitro micronucleus test (MNT) were performed. A high correlation was observed In each of the studies (>85%); however, no formal validation for the micronucleus In Vitro assay had been carried out. Therefore, a workIng group was established by the European Centre for the Validation of Alternative Methods (ECVAM) to perform a retrospective validation of the existIng data, In order to evaluate the validity of the In Vitro MNT on the basis of the modular validation approach. The primary focus of this retrospective validation was on the evaluation of the potential of the In Vitro MNT as alternative to the standard In Vitro CAT. The workIng group evaluated, In a first step, the available published data and came to the conclusion that two studies [German rIng trial, von der Hude, W., Kalweit, S., Engelhardt, G. et al. (2000) In-Vitro micronucleus assay with ChInese hamster V79 cells: results of a collaborative study with 26 chemicals. Mutat. Res., 468, 137-163, and SFTG International Collaborative Study, Lorge, E., Thybaud, V., Aardema, M., Oliver, J., Wataka, A., Lorenzon, G. and MarzIn, D. (2006) SFTG International Collaborative Study on In-Vitro micronucleus test I. General conditions and overall conclusions of the study. Mutat. Res., 607, 13-36] met the criteria for a retrospective validation accordIng to the criteria previously defIned by the workIng group. These two studies were evaluated In depth (IncludIng the reanalysis of raw data) and provided the Information required for assessIng the reliability (reproducibility) of the test. For the assessment of the concordance between the In Vitro MNT and the In Vitro CAT, additional published data were considered. Based on this retrospective validation, the ECVAM Validation Management Team concluded that the In Vitro MNT is reliable and relevant and can therefore be used as an alternative method to the In Vitro CAT. FollowIng peer review, these conclusions were formally endorsed by the ECVAM Scientific Advisory Committee.
