Evaluation of the micronucleus procedure over a 2-year period

Mutation Research/Reviews in Genetic Toxicology, 1983

Journal of carcinogenesis, 2005

As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue(R) mouse, and the lacZ model; commercially available as the Mutatrade markMouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it i...

Medical Journal of Indonesia, 1995

Mikronukleus adalah suatu bangunan bulat di dalan sitoplasnn, yang nrcngandu,tg ,,tassa kronatin (DNA). Mikrottukleus tinbul bila suatu populasi sel yang sedang nentbelah utengalatni patah kronosotn yang disebabknn oleh klastogen (sesuatu yang nrcnyebabknn patah krontoson), atau ntengalani hilangnT,a kronosour karena disfungsi spindel nitotilc IIji nikronukleus adalah cara cepat wûuk ntenguji nutagenisitas berbagai bahan. Uji itti juga dapat digunakan untuk nenilai kerusakan sitogenetikyang disebabkan paparan bahan genotoksik, dan telah terbukti satna sensitifnya dengan petneriksaan sitogenetik Makalah ini tnetnbicarakan tentang pene,,tuan mikronukleus, penyebab terbetûulaq,a nûkronukleus dan berbagai cspek uji nikronukleus. Mikronukleus dapat dianalisa pada berbagai sel, secarainvivo pada berbagai individu (nnnusia, hewan, dan tatranan), atau invitro padabiakan seI. Selyang paling sering diperiksa pada uji nùkronukleus itt vivo adalah eritrosit dan dan pada uji mikronukleus in vitro adabh linfosit. Penggunaan pewarnafluoresens pada uji nikronuHeus nentberi hasil yang lebih dapat dipercaya, tetapi penggunaannya terbatos, karena waktufluoresensinya terbatas.

Mutagenesis, 1992

This paper analyzes the mutagenicity results reported by the US National Toxicology Program (NTP), relative to 41 chemicals assayed with four in vitro short-term tests [Salmonella typhimurium (STY), Chromosomal aberrations in Chinese hamster ovary (CHO) cells (CHA), Sister chromatid exchange in CHO ceUs (SCE), mutation in L5178Y mouse lymphoma cells (MLY)] and puts this database in perspective with respect to other databases. It is shown that the test relationships pointed out by the experiments on the 41 chemicals are in substantial agreement with those indicated by a previous NTP report on 73 chemicals, and that the same test relationships were also indicated by the results on the International Program for the Evaluation of Short-Term Tests for Carcinogens (IPESTTC). The NTP and IPESTTC databases consistently indicated that there is a gradual increase in the sensitivity to the genotoxins in the following order: STY < CHA < SCE < MLY. On this scale, SCE and MLY show a great degree of similarity of responses to the chemicals, as does STY with CHA. The overall evidence provided by these results, and by the general pattern of IPESTTC and NTP genotoxicity profiles, does not support the notion that the genotoxic chemicals have genetic end point specificity. Moreover, a mathematical simulation analysis demonstrated that MLY and SCE-the two most sensitive assays of those studied by NTP-are not more subject to erratic results than other assays, and that they form-together with STY and CHA-a consistent family of genotoxicity assays.

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2011

Alternatives to Laboratory Animals, 2005

Mutagenesis, 2012

This paper presents a new curated database on in vivo micronucleus mutagenicity results, called ISSMIC. It is freely available at: http://www.iss.it/ampp/dati/cont.php?id5233&lang51&tipo57. The experimental results were critically reviewed, and evidence on target cell exposure was considered as well. The inspection of ISSMIC demonstrates that a large proportion of reported negative results in the literature (231 out 566 ISSMIC chemicals) lack a clear-cut, direct demonstration of toxicity at the target cells. Using this updated database, the predictive value of a compilation of Structural Alerts (SA) for in vivo micronucleus recently implemented in the expert system Toxtree was investigated. Individually, most of the SA showed a high Positive Predictivity ($80%), but the need for further expanding the list of alerts was pointed out as well. The role of in vivo micronucleus in strategies for carcinogenicity prediction was re-evaluated. In agreement with previous analyses, the data point to a low overall correlation with carcinogenicity. In addition, given the cost in animal lives and the time required for the experimentation, in many programs, the in vivo tests are used only to assess in vitro positive results. The ability of in vivo micronucleus to identify real positives (i.e. carcinogens) among chemicals positive in Salmonella or among chemicals inducing in vitro chromosomal aberrations was studied. It appears that the in vivo micronucleus test does not have added value and rather impairs the prediction ability of the in vitro tests alone. The overall evidence indicates that in vivo micronucleus-in its present form-cannot be considered an useful tool for routine genotoxicity testing but should be used in targeted mechanistic studies.

Journal of toxicology and environmental health

The universality of the genetic system in living organisms and the high experimental correlation between mutagenicity and carcinogenicity provide the rational basis for the use of mutagenicity in screening of possible carcinogens. The present genetic methodologies using microorganisms, cell cultures, Drosophila, and rodents are evaluated. No mutagenicity test can cover all aspects of tumor formation in the whole animal or human body, because each species and tissue has its own capacity for repair as well as balance of activation and deactivation mechanisms. The strategy of testing must vary, depending on the nature and use of the chemicals.

Mutagenesis, 2011

Chemosphere, 2013

h i g h l i g h t s " Arsenic genotoxicity was evaluated in Swiss albino mice through micronucleus assay. " Arsenic was found to induce marked increase in the frequency of micronucleated cells. " Increase in the frequency of micronucleated cells occurred in a dose dependent manner. " Significant genotoxicity was observed even at the human reference dose of arsenic.