The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Elisabeth Lorge - One of the best experts on this subject based on the ideXlab platform.
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genetic toxicity assessment employing the best science for human safety evaluation part ii performances of the in vitro micronucleus test compared to the mouse lymphoma assay and the in vitro Chromosome Aberration assay
Toxicological Sciences, 2007Co-Authors: Elisabeth Lorge, Carine Lambert, Veronique Gervais, Nathalie Becourtlhote, Jeanluc Delongeas, Nancy ClaudeAbstract:The in vitro micronucleus test is commonly used in the early stages of pharmaceutical development as a predictive tool for the regulatory mouse lymphoma assay or in vitro Chromosome Aberration test. The accumulated data from this assay leads to the suggestion that it could be used as an alternative to the Chromosome Aberration test or the mouse lymphoma assay in the regulatory genotoxicity battery. In this paper, we present the results of the in vitro micronucleus test on L5178Y mouse lymphoma cells with 25 compounds from Servier research and have compared these results to those obtained in the genotoxicity regulatory battery. All the negative compounds were also negative in the in vitro micronucleus assay. Among the 14 positive compounds, two of them, positive in the mouse lymphoma assay, were found negative in the in vitro micronucleus test. However, this apparent discordance was likely to be due to cytotoxicity- or high concentration-related false positive responses in the mouse lymphoma assay. In addition, we confirmed that the in vitro micronucleus assay is useful for detecting aneugens, especially, when cells in metaphasis and multinucleated cells are also scored and when cells are allowed to recover after the long treatment. On this series of compounds, the in vitro micronucleus assay showed high sensitivity and possibly a better specificity than the mouse lymphoma assay. Thus, the in vitro micronucleus assay was shown to be at least as adequate as the mouse lymphoma assay or the in vitro Chromosome Aberration test to be used in the standard genotoxicity battery.
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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, Silvio Albertini, Franziska Locher, Veronique Thybaud, 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.
B H Fu - One of the best experts on this subject based on the ideXlab platform.
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follow up study by Chromosome Aberration analysis and micronucleus assays in victims accidentally exposed to 60co radiation
Health Physics, 2010Co-Authors: Y M Lu, L P Jiang, B H Fu, Bingli Jiang, Feng Ling Zhao, En Hai Jiang, Xu SuAbstract:The goal of this study was to assess the persistence of chromosomal Aberrations and micronuclei of three victims 2 y after accidental radiation exposure to Co gamma rays. Traditional Chromosome Aberration analysis was performed by scoring the dicentric Chromosomes (dic) and rings (r) in peripheral blood lymphocytes. Micronuclei were detected using the cytokinesis block micronucleus assay. G-banding and semi-automatic karyotype analysis was used to record translocations (t), inversions (inv) and deletions (del). The frequency of unstable chromosomal Aberrations (dicentrics and rings) remained at high levels 6 mo after the accident. Two years after exposure, the frequency was reduced to 4-11% in the three victims. However, stable Chromosome Aberrations, which were detected by G-banding and included t, inv, and del, remained at a high level and have an obvious dose-dependent relationship even 2 y post-exposure. The frequency of micronuclei decreased faster than that of Chromosome Aberrations, reaching almost a normal level two years after the accident, especially for the child victim. Unstable Chromosome Aberrations reduced gradually, but the stable Aberration remained at a high level along with the time-lapse. The micronucleus assay was less valuable for assessing long-term effects after high dose irradiation. Language: en
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dose estimation by Chromosome Aberration analysis and micronucleus assays in victims accidentally exposed to 60co radiation
British Journal of Radiology, 2009Co-Authors: Z Q Wang, Y M Lu, Q L Huang, W Z Zhao, J Li, L P Jiang, W S Tang, B H FuAbstract:The objective of this study was to assess the radiation exposure levels in victims of a 60Co radiation accident using Chromosome Aberration analysis and the micronucleus assay. Peripheral blood samples were collected from three victims exposed to 60Co 10 days after the accident and were used for the Chromosome Aberration and micronucleus assays. After in vitro culture of the lymphocytes, the frequencies of dicentric Chromosomes and rings (dic+r) and the numbers of cytokinesis blocking micronuclei (CBMN) in the first mitotic division were determined and used to estimate radiation dosimetry. The Poisson distribution of the frequency of dic+r in lymphocytes was used to assess the uniformity of the exposure to 60Co radiation. Based on the frequency of dic+r in lymphocytes, estimates of radiation exposure of the three victims were 5.61 Gy (A), 2.48 Gy (B) and 2.68 Gy (C). The values were estimated based on the frequencies of CBMN, which were 5.45 Gy (A), 2.78 Gy (B) and 2.84 Gy (C). The estimated radiation dos...
Y M Lu - One of the best experts on this subject based on the ideXlab platform.
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follow up study by Chromosome Aberration analysis and micronucleus assays in victims accidentally exposed to 60co radiation
Health Physics, 2010Co-Authors: Y M Lu, L P Jiang, B H Fu, Bingli Jiang, Feng Ling Zhao, En Hai Jiang, Xu SuAbstract:The goal of this study was to assess the persistence of chromosomal Aberrations and micronuclei of three victims 2 y after accidental radiation exposure to Co gamma rays. Traditional Chromosome Aberration analysis was performed by scoring the dicentric Chromosomes (dic) and rings (r) in peripheral blood lymphocytes. Micronuclei were detected using the cytokinesis block micronucleus assay. G-banding and semi-automatic karyotype analysis was used to record translocations (t), inversions (inv) and deletions (del). The frequency of unstable chromosomal Aberrations (dicentrics and rings) remained at high levels 6 mo after the accident. Two years after exposure, the frequency was reduced to 4-11% in the three victims. However, stable Chromosome Aberrations, which were detected by G-banding and included t, inv, and del, remained at a high level and have an obvious dose-dependent relationship even 2 y post-exposure. The frequency of micronuclei decreased faster than that of Chromosome Aberrations, reaching almost a normal level two years after the accident, especially for the child victim. Unstable Chromosome Aberrations reduced gradually, but the stable Aberration remained at a high level along with the time-lapse. The micronucleus assay was less valuable for assessing long-term effects after high dose irradiation. Language: en
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dose estimation by Chromosome Aberration analysis and micronucleus assays in victims accidentally exposed to 60co radiation
British Journal of Radiology, 2009Co-Authors: Z Q Wang, Y M Lu, Q L Huang, W Z Zhao, J Li, L P Jiang, W S Tang, B H FuAbstract:The objective of this study was to assess the radiation exposure levels in victims of a 60Co radiation accident using Chromosome Aberration analysis and the micronucleus assay. Peripheral blood samples were collected from three victims exposed to 60Co 10 days after the accident and were used for the Chromosome Aberration and micronucleus assays. After in vitro culture of the lymphocytes, the frequencies of dicentric Chromosomes and rings (dic+r) and the numbers of cytokinesis blocking micronuclei (CBMN) in the first mitotic division were determined and used to estimate radiation dosimetry. The Poisson distribution of the frequency of dic+r in lymphocytes was used to assess the uniformity of the exposure to 60Co radiation. Based on the frequency of dic+r in lymphocytes, estimates of radiation exposure of the three victims were 5.61 Gy (A), 2.48 Gy (B) and 2.68 Gy (C). The values were estimated based on the frequencies of CBMN, which were 5.45 Gy (A), 2.78 Gy (B) and 2.84 Gy (C). The estimated radiation dos...
Xu Su - One of the best experts on this subject based on the ideXlab platform.
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follow up study by Chromosome Aberration analysis and micronucleus assays in victims accidentally exposed to 60co radiation
Health Physics, 2010Co-Authors: Y M Lu, L P Jiang, B H Fu, Bingli Jiang, Feng Ling Zhao, En Hai Jiang, Xu SuAbstract:The goal of this study was to assess the persistence of chromosomal Aberrations and micronuclei of three victims 2 y after accidental radiation exposure to Co gamma rays. Traditional Chromosome Aberration analysis was performed by scoring the dicentric Chromosomes (dic) and rings (r) in peripheral blood lymphocytes. Micronuclei were detected using the cytokinesis block micronucleus assay. G-banding and semi-automatic karyotype analysis was used to record translocations (t), inversions (inv) and deletions (del). The frequency of unstable chromosomal Aberrations (dicentrics and rings) remained at high levels 6 mo after the accident. Two years after exposure, the frequency was reduced to 4-11% in the three victims. However, stable Chromosome Aberrations, which were detected by G-banding and included t, inv, and del, remained at a high level and have an obvious dose-dependent relationship even 2 y post-exposure. The frequency of micronuclei decreased faster than that of Chromosome Aberrations, reaching almost a normal level two years after the accident, especially for the child victim. Unstable Chromosome Aberrations reduced gradually, but the stable Aberration remained at a high level along with the time-lapse. The micronucleus assay was less valuable for assessing long-term effects after high dose irradiation. Language: en
Nancy Claude - One of the best experts on this subject based on the ideXlab platform.
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genetic toxicity assessment employing the best science for human safety evaluation part ii performances of the in vitro micronucleus test compared to the mouse lymphoma assay and the in vitro Chromosome Aberration assay
Toxicological Sciences, 2007Co-Authors: Elisabeth Lorge, Carine Lambert, Veronique Gervais, Nathalie Becourtlhote, Jeanluc Delongeas, Nancy ClaudeAbstract:The in vitro micronucleus test is commonly used in the early stages of pharmaceutical development as a predictive tool for the regulatory mouse lymphoma assay or in vitro Chromosome Aberration test. The accumulated data from this assay leads to the suggestion that it could be used as an alternative to the Chromosome Aberration test or the mouse lymphoma assay in the regulatory genotoxicity battery. In this paper, we present the results of the in vitro micronucleus test on L5178Y mouse lymphoma cells with 25 compounds from Servier research and have compared these results to those obtained in the genotoxicity regulatory battery. All the negative compounds were also negative in the in vitro micronucleus assay. Among the 14 positive compounds, two of them, positive in the mouse lymphoma assay, were found negative in the in vitro micronucleus test. However, this apparent discordance was likely to be due to cytotoxicity- or high concentration-related false positive responses in the mouse lymphoma assay. In addition, we confirmed that the in vitro micronucleus assay is useful for detecting aneugens, especially, when cells in metaphasis and multinucleated cells are also scored and when cells are allowed to recover after the long treatment. On this series of compounds, the in vitro micronucleus assay showed high sensitivity and possibly a better specificity than the mouse lymphoma assay. Thus, the in vitro micronucleus assay was shown to be at least as adequate as the mouse lymphoma assay or the in vitro Chromosome Aberration test to be used in the standard genotoxicity battery.