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FDA/CFSAN Redbook 2000 IV.C.1.d. Mammalian Erythrocyte Micronucleus Test This in vivo micronucleus test is used for the detection of damage induced by the test substance to the chromosomes or the mitotic apparatus of erythroblasts by analysis of erythrocytes as sampled in bone marrow and/or peripheral blood cells of animals, usually rodents. The purpose of the micronucleus test is to identify substances that cause cytogenetic damage which results in the formation of micronuclei containing lagging chromosome fragments or whole chromosomes. Positive results in the micronucleus test indicate that a substance induces micronuclei, which are the result of chromosomal damage or damage to the mitotic apparatus in the erythroblasts of the test species. vm.cfsan.fda.gov /~redbook/redivc1d.html   (5021 words)

NTP: Micronucleus The micronucleus test is performed in a variety of ways, depending upon the questions the investigator is attempting to answer, the test organism, the cell type that is assayed, and the mode of action of the chemical. For the micronucleus frequency in any dose group to be considered significantly elevated over the control group, the P value must be equal to or less than 0.025 divided by the number of chemical-treatment groups. The final conclusion for a micronucleus test is determined by considering the results of statistical analyses, the reproducibility of any observed effects, and the magnitude and biological significance of those effects. ntp-server.niehs.nih.gov /index.cfm?objectid=070CC011-C29C-6943-54274A45E042F7CC   (1251 words)

Micronucleus and Sister Chromatid Exchange Frequency in Endemic Fluorosis Micronucleus rates: The mean value of the MN was 1.94 + 0.86% in the patients with fluorosis and the range value was 1-15%, which was much higher than the mean value of 0.57 + 0.44% in the controls and the mean value of 1.05 + 0.68% in the healthy exposed people. The appearance of the micronucleus in peripheral blood indicates that fluorine may be a mutagenic agent. Hence we conclude that the micronucleus experiment can be used as a testing procedure to detect fluorosis, with fluoride being one of the dangerous factors inducing mutagenesis. www.fluoridealert.org /sce-fluorosis.htm   (1113 words)

article 3 Hydroquinone was slightly positive in the micronucleus and the chromosome aberration assay and it revealed distinct effects in the mouse lymphoma test. The cytochalasin-block micronucleus test, the sister chromatid exchange test and the alkaline elution technique were compared in their ability to detect genetic damage in human peripheral lymphocytes in a case of an elevated occupational exposure with antineoplastic agents. In conclusion, the cytochalasin-block micronucleus test seems to be a rapid, highly sensitive and specific tool for biological exposure monitoring in comparison to the classically established sister chromatid exchange test and alkaline elution. www.swan.ac.uk /cget/ejgt/article3.htm   (16934 words)

Ultra High Speed Automated In-Vitro Micronucleus Analysis - 050701150203   (Site not responding. Last check: 2007-11-04) Micronucleus induction is a key characteristic of genotoxic compounds. Analysis of micronucleus formation resulting from DNA strand breakage or interference with chromosome segregation is an important component of toxicology screening of new drug candidates. Manual scoring of micronucleus assays is time consuming and subject to operator variance, bias and error. www.sbsonline.org /sbscon/2005/posters/050701150203.php   (162 words)

Micronucleus Testing at Litron   (Site not responding. Last check: 2007-11-04) The in vivo micronucleus test is used to screen test articles for clastogenic (chromosome-breaking) and aneugenic (loss of whole chromosome) activity. The test is based on the observation that mitotic cells with chromosome breaks exhibit disturbances in the anaphase distribution of their chromatin. Following Litron’s protocol for the Mouse Micronucleus Test, a chemical, formulation or extract is evaluated for its ability to induce cytogenetic damage in mouse erythrocyte precursor cells, resulting in the formation of MN. www.litronlabs.com /test_micronucleus2.asp   (231 words)

article 4 The inclusion of a tumorsupressorgene in the micronucleus and the subsequent inactivation or loss of that micronucleus could lead to a transformed cell and therefore be a step in carcinogenesis. Reintegration of micronuclear material is theoretically possible, but would require the micronucleus to be in cycle with the main nucleus to be successful; otherwise the result may be premature chromosome condensation in the micronucleus and subsequent destruction of that DNA (Obe et al. In the case of clastogenic compounds the loss of the material in micronuclei may not be quite as detrimental to the cell and mutants might be formed through the hypothesized pathway. www.swan.ac.uk /cget/ejgt/article4.htm   (3629 words)

The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for ...   (Site not responding. Last check: 2007-11-04) The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for tumour radiocurability The study of cellular radiosensitivity in vitro was conducted in parallel with the study of cellular damage after tumour irradiation in vivo. Our results suggest that evaluation of increment of micronucleus frequency during radiotherapy (after fixed tested dose of 20 Gy) offers a potentially valuable approach to predicting individual radioresponsiveness and may be helpful for individualization of treatment strategy in advanced stage cervical cancer. www.nature.com /bjc/journal/v80/n10/abs/6690569a.html   (359 words)

Study on the Toxicology of FRC001 (China No.1 Tian Xian Liquid)   (Site not responding. Last check: 2007-11-04) It is generally thought that the occurance of micronucleus in interphase caused by mutagen, i.e, the micronucleus consists of the pieces of chromosome after the acting of mutagen. The positive of micronucleus test and sperm aberration test of FRC001 may be related to its ingredients, the interaction of ingredients and /or the formation of new products during the preparation of FRC001. Micronucleus method for detertion of meiosis micronuclei in male germ cells of mammals. www.tianxian.com /science/toxicology.asp   (2151 words)

Literatur   (Site not responding. Last check: 2007-11-04) Fenech, M. (1993): The cytokinesis-block micronucleus technique: A detailed description of the method and its application to genotoxicity studies in human populations. Braithwaite, I. and Ashby J. (1988): A non-invasive micronucleus assay in the rat liver. Renzi, L., Pacchierotti, F. and Russo, A. (1996): The centromere as a target for the induction of chromosome damage in resting and proliferating mammalian cells: assessment of mitomycin C-induced genetic damage at kinetochores and centromeres by a micronucleus test in mouse splenocytes. www.uni-kl.de /FB-Biologie/AG-Zankl/mnlit.htm   (2200 words)

Automated Micronucleus Assays from Cellomics - Biocompare Product Showcase   (Site not responding. Last check: 2007-11-04) The Micronucleus BioApplication is a powerful image analysis algorithm for identifying and quantitating the rare event of micronucleus formation as a measure of genotoxicity... The Micronucleus BioApplication is a flexible, specific, multi-channel, High Content Screening (HCS) software module that enables automated analysis of genotoxicity by examining the frequency of micronucleus formation in single cells. Quantitative results for multiple conditions can be quickly obtained with this automated format, as shown in the dose-response of micronucleus induction for bleomycin and mitomycin C. In addition to genotoxicity, the Micronucleus BioApplication automatically determines the ratio of multinucleated to mononucleated cells for monitoring cell-cycle delay, an early indicator of cytotoxicity. www.biocompare.com /showcase.asp?id=27   (458 words)

Mitotic Disturbances and Micronucleus Induction in Syrian Hamster Embryo Fibroblast Cells Caused by Asbestos Fibers The following endpoints were investigated: micronucleus formation as a result of mitotic disturbances and characterization of the induced micronucleus population by kinetochore staining and visualization of the spindle apparatus. The results of the micronucleus assay showed that chrysotile, crocidolite, and amosite induce micronuclei in SHE cells in a dose-dependent manner. The maximum micronucleus frequency triggered by amosite (>250 MN/2000 cells) is the highest of all compounds tested in the SHE cell-system so far. www.ehponline.org /members/1995/103-3/dopp-full.html   (2586 words)

Tian Xian - Cancer Alternative Treatment   (Site not responding. Last check: 2007-11-04) Generally in the micronucleus test, the micronucleus rate of cyclophosphamide (positive control group) is 0~3%, the micronucleus rate of negative control group is lower than 3%. According to Figure 3,4, the micronucleus rate of positive control group and negative control group were 30.3% and 1.4%, respectively. The micronucleus rate of low, middle and high dose of FRC001 were 4.5%, 6.6%, 9.0%, respectively, The difference between Edfrnn groups and negative control group were significant. www.tian-xian.com /lab-result1.asp   (2324 words)

Links   (Site not responding. Last check: 2007-11-04) Important variables that influence base-line micronucleus frequency in cytokinesis-blocked lymphocytes - a biomarker for DNA damage in human populations The position of the in vitro micronucleus test within the battery of screening for genotoxic potencial determination and the regulatory guidelines The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously mitotic delay, apoptosis, chromosome breakage, chromosome loss and non-disjunction www.icb.ufmg.br /~prodap/2003/micronucleos/artigos.html   (105 words)

Micronucleus investigation of alcoholic patients with oral carcinomas The micronucleus test (MN) is used as an indicator of genotoxic exposition, since it is associated with chromosome aberrations. A micronucleus (MN) is a small extranucleus separated from the main one, generated during cellular division by late chromosomes or by chromosome fragments. Because of its association with chromosomal aberrations, MN have been used since 1937 as an indicator of genotoxic exposition based on the radiation studies conducted by Brenneke and Mather (Heddle et al., 1983). www.funpecrp.com.br /gmr/year2002/vol3-1/gmr0038_full_text.htm   (4323 words)

Homocysteine The micronucleus index of these men (n = 34) in cytokinesis-blocked binucleated cells (19.2 +/- 1.1) was significantly elevated (P = 0.02) when compared to the micronucleus index of the rest of the men who had normal levels of folate, vitamin B12 and homocysteine (16.3 +/- 1.3, n = 30). Interestingly, the micronucleus index in men with normal folate and vitamin B12, but homocysteine levels >10 mu mol/l (19.4 +/- 1.7, n = 15) was also significantly higher (P = 0.05) when compared to those with normal folate, vitamin B12 and homocysteine. The micronucleus index was not significantly correlated with folate indices, but there was a significant (P = 0.013) negative correlation with serum vitamin B12 (r(2) = 0.099). www.lef.org /protocols/abstracts/abstr-txt/abst-hom.html   (861 words)

Hot Topics! Small RNAs May Cause Genomic Rearrangements in Tetrahymena The diploid and transcriptionally inert micronucleus, on the other hand, acts as the germline nucleus during conjugation. The diploid micronucleus of each of these two cells then divides by meiosis--three of the meiotic products are destroyed, while the remaining one undergoes a mitotic division to produce two identical zygotic nuclei in each mating cell. The scan RNAs would subsequently be transferred from the old micronucleus to the old macronucleus (where IES elimination and chromosome breakage have already taken place)--this transfer could possibly be mediated via TWI1. www.ambion.com /techlib/hottopics/scnRNA_10042002.html   (962 words)

Statute: § 79.64 In vivo micronucleus assay. The micronucleus assay is an in vivo cytogenetic test which uses erythrocytes in the bone marrow of rodents to detect chemical damage to the chromosomes or mitotic apparatus of mammalian cells. As the erythroblast develops into an erythrocyte (red blood cell), its main nucleus is extruded and may leave a micronucleus in the cell body; a few micronuclei form under normal conditions in blood elements. This assay is based on an increase in the frequency of micronucleated erythrocytes found in bone marrow from treated animals compared to that of control animals. www.arb.ca.gov /bluebook/bb05/40cfr/40cfr79_64.htm   (1161 words)

In vivo chromosome damaging effects of an inosine monophosphate dehydrogenase inhibitor: Ribavirin in mice Seetharama ... Besides, the previous studies in mice have employed multiple treatments [12] or the exposure of very high doses [13] and the toxicity was evaluated by the micronucleus test. The bone marrow micronucleus test has been a most suitable genotoxicity test [24] along with simultaneously used tests like chromosome aberration, peripheral blood micronucleus and sperm morphology tests. The results from the peripheral blood micronucleus test further indicated that the responses of MNPCEs were totally different from that of the bone marrow. www.ijp-online.com /article.asp?issn=0253-7613;year=2005;volume=37;issue=2;spage=90;epage=95;aulast=Seetharama   (3166 words)

Comparative Activity of Human Carcinogens and NTP Rodent Carcinogens in the Mouse Bone Marrow Micronucleus Assay: An ... By displaying the high sensitivity of the micronucleus assay to the reference human and rodent genotoxins, this analysis emphasizes the weakness in the MN assay responses given by the NTP carcinogens reported by Shelby et al. The oral micronucleus data for benzene (6) are added to Table 1 to contrast with the intraperitoneal injection study results reported by Shelby et al. Tinwell H, Ashby J. Micronucleus morphology as a means to distinguish aneugens and clastogens in the mouse bone marrow micronucleus assay. ehp.niehs.nih.gov /members/1994/102-9/tinwell-full.html   (3562 words)

Automated Micronucleus Assay System - Micronucleus Scoring Validation Test: Accuracy, Repeatability The system was set up to identify micronuclei that met the following criteria: 1) the micronucleus must be in the same plane as the cells, 2) the micronucleus must be round or oval, 3) the micronucleus must be contained within the cell membrane (i.e. If we had any questions as to whether the potential micronucleus found was truly a micronucleus, we removed it from the MPCE count. In addition to the benefits of increased compound testing throughput and increased objectivity and quantitative repeatability of scoring, the LAI Automated Micronucleus Assay system also provides the ability to view quantitative data that is not available when using manual methods of scoring. www.loats.com /docs/MNvalid/MNvalid.htm   (2076 words)

DEVELOPMENT OF A NOVEL MICRONUCLEUS ASSAY USING THE HUMAN 3-D SKIN MODEL, EPIDERM™. Summary: The rodent in vivo micronucleus assay is an important part of a tiered testing strategy in genetic toxicology. Although in vivo rodent skin micronucleus assays are being developed, the results will still require extrapolation to the human. We first evaluated whether a population of binucleated cells sufficient for a micronucleus assay could be obtained by expos-ing the tissue to 1-3 ug/ml cytochalasin B (Cyt B). www.mattek.com /pages/abstracts/358   (393 words)

Indian Journal of Pharmacology: In vivo chromosome damaging effects of an inosine monophosphate dehydrogenase ...   (Site not responding. Last check: 2007-11-04) The genotoxic effects of ribavirin are not exerted in a dose-dependent pattern in mouse. Moreover, the micronucleus or sperm morphology tests have limitations as they are unable to identify the type of chromosomal damage induced. If this test is conducted along with bone marrow micronucleus test and chromosome aberration test, the accuracy of genotoxicity evaluation is 100%. findarticles.com /p/articles/mi_m0RUE/is_2_37/ai_n13603885   (1020 words)

LAI's Automated Micronucleus Assay System The micronucleus assay is one of the most widely used tests for mutagenesis and potential carcinogenesis required by regulatory agencies for testing of genetic toxicity in regulated substances, during pre-clinical assessment of pharmaceuticals. Results of actual pharmaceutical laboratory use of the LAI Micronucleus Assay System show a 75% reduction in man-hours required for scoring of a Micronucleus Assay for a single compound. Manual interaction is only required to load the slides onto the stage or into the slide delivery system, and for editing the potentially micronucleated cells after the slides have been automatically scored by the system. www.loats.com /mnu3.html   (783 words)

Mouse Micronucleus Assay The mouse bone-marrow micronucleus assay measures the ability of a test article to induce chromosome damage in whole animals. Compounds or extracts of medical devices can be administered orally, intraperitoneally, or intravenously as single or multiple doses. Micronucleus assays can be customized to meet customer requirements or can follow our generic protocols, which include the following: www.hessinc.cc /micronucleus.htm   (66 words)

Induced Micronucleus Frequencies in Peripheral Lymphocytes as a Screening Test for Carriers of a BRCA1 Mutation in ... Induced Micronucleus Frequencies in Peripheral Lymphocytes as a Screening Test for Carriers of a BRCA1 Mutation in Breast Cancer Families -- Rothfuss et al. Nucleoplasmic bridges are a sensitive measure of chromosome rearrangement in the cytokinesis-block micronucleus assay Correspondence re: A. Rothfuss et al., Induced micronucleus frequencies in peripheral blood lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families. cancerres.aacrjournals.org /cgi/content/abstract/60/2/390   (902 words)

Results During this stage, the micronucleus is a discrete organelle in close physical contact with the macronucleus. 4 The micronucleus has begun moving away from the macronucleus in preparation for division. Chromosomes align in the center of the micronucleus. www.stolaf.edu /people/schneidb/Results.html   (547 words)

Micronucleus Calculation for Radiotherapy of Head and Neck Tumor   (Site not responding. Last check: 2007-11-04) Objective: To study micronucleus (MN) calculation in exfoliated cells of the oral mucosa before and after radiotherapy for head and neck tumor. Method: 30 patients after radiotherapy for head and neck tumor, 30 patients during radiotherapy for head and neck tumor, and 30 healthy individuals in control group were concluded in this study. We also suggest that the calculation of micronucleus number of exfoliated cells could be used in monitoring recurrence of head and neck cancer after radiation. iadr.confex.com /iadr/2005Balt/techprogram/abstract_62227.htm   (354 words)

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