Chromosomal damage micronucleus test

Damage induced in whole animals can be detected in in vivo chromosome assays in either somatic or germinal cells by examination of metaphases or the formation of micronuclei. The micronucleus test can also detect whole chromosome loss or aneuploidy in the absence of clastogenic activity and is considered comparable in sensitivity to chromosome analysis (Tsuchimoto and Matter, 1979). 

The in vivo micronucleus test is used for the detection of damage to chromosomes as well as the mitotic apparatus in bone marrow or peripheral blood cells of rodents. The assay system has been well standardized.14-17 The basic features of the test system are (1) the effect of the test chemical is observed in anucleated polychromatic erythrocytes (PCEs) (2) PCEs have a relatively short lifespan, so that any micronuclei they contain must have been generated as a result of recently induced chromosome damage (3) micronuclei are readily identifiable and their distribution is well defined and (4) the frequency of induced micronuclei in PCEs is dependent on sampling times. 

Positive results in the mammalian in vivo erythrocyte micronucleus test indicate that a substance produces micronuclei in the immature erythrocytes of the test species, which are the result of chromosomal damage or damage to the mitotic apparatus in the erythroblasts of the test species. 

Positive results from the in vitro micronucleus test indicate that the test substance induces chromosome damage and/or damage to the cell division apparams, in cultured mammahan somatic cells. Immunochemical labehng (FISH fluorescence in sim hybridization) of kinetochores, or hybridization with general or chromosome specific centromeric/telomeric probes can provide useful information on the mechanism of micronucleus formation. Use of cytokinesis block facilitates the acquisition of the additional mechanistic information (e.g., chromosome nondisjunction) that can be obtained by FISH techniques. The micronucleus assay has a number of advantages over metaphase analysis performed to measure chromosome aberrations (see OECD TG 487 draft). 

Mackay JM, Fox V, Griffiths K, et al Trichloroacetic acid Investigation into the mechanism of chromosomal damage in the in vitro human lymphocyte cytogenetic assay and the mouse bone marrow micronucleus test. Carcinogenesis 16(5) 1127-1133, 1995... 

CS has been tested for its capacity to induce mutations in bacteria and in the fruit fly Drosophila melanogaster and for its capacity to cause chromosomal damage, as measured by a micronucleus test, in mice. Its capacity to bind to DNA in mammalian liver and kidney has also been studied. The results have been predominantly negative. 

CS has been tested for its ability to cause chromosomal damage in a micronucleus test in mice. Micronucleus tests detect small nuclei that arise from chromosomal fragments or chromosomes that fail to be incorporated into normal daughter nuclei when cells divide. An increased frequency of micronuclei is evidence of chromosomal break-... 

Bis(bromomethyl)propane-l,3-diol was mutagenic in only one of several bacterial strains tested, and only with metabolic activation. In cultured mammalian cells, it was only weakly active in tests for chromosomal aberrations and sister chromatid exchanges. Micronucleus formation, indicative of chromosomal damage, was induced in cells from mice exposed to 2,2-bis(bromomethyl)propane-l,3-diol in vivo. 

Mi ce Micronucleus test cytotoxic doses highest 125 mg/kg body weight - (no evidence of chromosomal damage or malfunction) Schwei nfurth Gunzel 1987 and... 

Cytogenetic damage Mouse Micronucleus test Chromosomal fragments in erythrocyte stem cells <1 mo M M M M... 

The in vitro micronucleus test (MNvit) represents a reliable and relevant alternative to the CAvit for the assessment of genetic damage to chromosomes, in the form of either clastogenic (chromosome break) or aneugenic (whole chromosome) events, as shown by the EURL ECVAM retrospective validation study [57-60],... 

Until recently, most regulatory guidelines have focused mainly on tests for gene mutations and structural chromosome damage. HowevCT, the validation of the in vitro micronucleus test and the development of an OECD gnideline indicates that its use will become much more widespread (OECD 2007). 

Purpose. The purpose of the in vivo micronucleus test is to evaluate the potential of the test substance to cause chromosomal damage (clastogenicity) or damage to the mitotic apparatus (aneugenicity) by the analysis of micronuclei in erythrocytes sampled in bone marrow and/or in peripheral blood of experimental animals (usually rodents) (Schmid 1975 Heddle 1973 Heddle and Salamone 1981). 

Even if the bone marrow is a well-perfused tissue, chemically unstable compounds and/or metabolites may not reach it in sufficient quantities to induce detectable effects (Brambilla and Martelli 2004 Morita et al. 1997). In a large collaborative study of I ARC carcinogens (groups 1, 2A, and 2B), the in vivo bone marrow micronucleus test easily detected compounds able to induce tumors in hematopoietic tissues and lung. In contrast, it predicted only 40% of liver carcinogens (Morita et al. 1997). To solve this issue, chromosome damage, especially micronuclei, can be measured in tissues other than bone marrow and peripheral blood erythrocytes (Hayashi et al. 2007). 

B12, known as the "micronucleus test", is also for the study of chromosomal damage. It is based on an increase in the number of micronuclei in the polychromatic erythrocytes of animals treated with the test substance in relation to a control group. 

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