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      The micronucleus test—most widely used in vivo genotoxicity test—

      review-article
      Genes and Environment
      BioMed Central
      Micronucleus, Historical consideration, Chromosomal aberration, in vivo, Animal welfare

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          Abstract

          Genotoxicity is commonly evaluated during the chemical safety assessment together with other toxicological endpoints. The micronucleus test is always included in many genotoxic test guidelines for long time in many classes of chemicals, e.g., pharmaceutical chemicals, agricultural chemicals, food additives. Although the trend of the safety assessment of chemicals faces to animal welfare and in vitro systems are more welcome than the in vivo systems, the in vivo test systems are paid more attention in the field of genotoxicity because of its weight of evidence. In this review, I will summarize the following points: 1) historical consideration of the test development, 2) characteristics of the test including advantages and limitations, 3) new approaches considering to the animal welfare.

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          Most cited references46

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          The micronucleus test.

          W. Schmid (1975)
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            Measurement of micronuclei in lymphocytes.

            The micronucleus technique has been proposed as a method for measurement of chromosomal damage in mitogen-stimulated human lymphocytes. Micronuclei require one cell division to be expressed and, consequently, the conventional micronucleus technique is very imprecise since the cells which have undergone only one division, and the micronuclei in them, cannot be identified separately from the total population of lymphocytes. To overcome this problem, two methods were developed to identify cells which have undergone their first mitosis. Using an autoradiographic technique, lymphocytes were pulse-labelled with [3H]thymidine at 48 h of culture, allowed to proceed through mitosis, identified by autoradiography between 72 and 84 h and micronuclei were scored in them. It was not possible to select a concentration of radiolabel which did not itself produce micronuclei and consequently the method was of no value for measuring pre-existing chromosomal damage present in vivo. However, it was capable of quantitating micronuclei produced by irradiation of lymphocytes in vitro. In the second method, cytokinesis was blocked using cytochalasin B. Micronuclei were scored in cytokinesis-blocked cells. These were easily recognisable owing to their binucleate appearance and a large number could be accumulated by adding 3.0 micrograms/ml cytochalasin B at 44 h and scoring at 72 h. Cytochalasin B did not itself produce micronuclei. The cytokinesis-block method was simple to perform; the 'in vivo' micronucleus frequency in normal individuals was 4.4 +/- 2.6 micronuclei/500 cytokinesis-blocked cells; and for lymphocytes irradiated in vitro there was a linear relationship between dose of radiation and number of induced micronuclei. The cytokinesis-block method appears to be the procedure of choice for quantitating micronuclei in lymphocytes.
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              A rapid in vivo test for chromosomal damage.

              J A Heddle (1973)
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                Author and article information

                Contributors
                makoto_hayashi@wine.ocn.ne.jp
                Journal
                Genes Environ
                Genes Environ
                Genes and Environment
                BioMed Central (London )
                1880-7046
                1880-7062
                1 October 2016
                1 October 2016
                2016
                : 38
                : 18
                Affiliations
                makoto international consulting (mic), Kami-imaizumi, Ebina, Kanagawa 243-0431 Japan
                Article
                44
                10.1186/s41021-016-0044-x
                5045625
                27733885
                275006d4-9223-4d93-a81e-04b49eee27fb
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 April 2016
                : 4 May 2016
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                micronucleus,historical consideration,chromosomal aberration,in vivo,animal welfare

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