Micronucleus assay

In a micronucleus assay using male B6C3Fj mice dosed with 0, 250, 500, or 1,000 mg/kg diisopropyl methylphosphonate, a small but significant increase in micronuclei were observed at mid- and high-dose levels (DOD 1991a). However, the maximum response was found to be within the laboratory historical control limits. The assay was repeated and the increase in micronuclei was not observed, therefore, it is believed that diisopropyl methylphosphonate did not cause micronuclei induction in this experiment. Diisopropyl methylphosphonate was also negative for the induction of micronuclei in the rat bone marrow after administration of up to 800 mg/kg (DOD 1991b). 

The platform includes different decision trees for the following endpoints the estimation of Threshold of Toxicological Concern (TTC), aquatic modes of action [44], skin and eye irritation and corrosion, mutagenicity and carcinogenicity [45], in vivo micronucleus assay, identification of Michael Acceptors and biodegradation potential [46]. 

In the latest version of Toxtree, another rulebase has been implemented for the in vivo micronucleus assay (ToxMic rulebase) which identifies 30 SAs from the Benigni-Bossa rulebase for genotixic carcinogenicity and five alerts specific for the micronucleus assay [47], The occurrence of micronucleus in cells, tissue, or blood is linked to irreversible mutations which can also lead to cancer. 

Response Note Benigni Bossa rulebase for carcinogenicity Response SAs for in vivo micronucleus assay in rodents Response... 

PFTA Non Positive Compound is out of model Applicability Domain No alerts for carcinogenic activity Positive SAs for the micronucleus assay... 

Benigni R, Bossa C, Tcheremenskaia O, Worth A (2009) Development of structural alerts for the in vivo micronucleus assay in rodents. European Commission Report EUR 23844 EN... 

Aniline gave positive responses in the mouse bone-marrow micronucleus assay when administered via ingestion or intraperitoneal injection (Ashby et al. 1991 Westmoreland and Gatehouse 1991). However, the positive responses occurred only at a specific time after administration and at what the authors considered high doses (1,000 mg/kg orally and 300 mg/kg intraperitoneally). 

Ashby, J., D.A.Vlachos, and H.Tinwell. 1991. Activity of aniline in the mouse bone marrow micronucleus assay. Mutat. Res. 263 115—117. 

Vlachos, D.A. 1988. Mouse Bone Marrow Micronucleus Assay of FC-141b. Haskell Laboratory Report No. 746-88. E.I. du Pont de Nemours and Company, Inc., Newark, DE. 

Benigni R. 1995. Mouse bone marrow micronucleus assay Relationships with in vitro mutagenicity and rodent carcinogenicity. J Toxicol Environ Health 45 337-347. 

The micronucleus assay may be used not only for the detection of acute but also chronic genetic damage. In mice, chromosomal breakage in bone marrow erythroblasts produces an accumulation of micronuclei in normochromatic erythrocytes in peripheral blood and there is little, if any, selective removal of micronucleated cells from circulation. This is not the case with rats, which limits their usefulness in long-term studies using peripheral blood. 

Hayashi, M., Morita, T., Kodama, Y., Sofuni, T., and Ishidate, Jr, M., The micronucleus assay with peripheral blood reticulocytes using acridine-coated slides, Mutat. Res., 245, 245,1990. 

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). 

Acetonitrile was not mutagenic in Salmonella typhimurium assays, with or without metabolic activation." Positive results were obtained in a micronucleus assay, and weakly positive responses for sister chromatid exchanges and chromosomal aberrations occurred in Chinese hamster ovary cells." ... 

Benzyl chloride caused genetic mutations and chromosome-damaging effects in a wide variety of in vitro assays it was not mutagenic in vivo in the mouse micronucleus assay. ... 

Charles JM, Cunny HC, Wilson RD, et al In vivo micronucleus assays on 2,4-dichlorophenoxyacetic acid and its derivatives. Mutat Res 444 227-34,1999... 

Morita T, Hayashi M 1,4-Dioxane is not mutagenic in five in vitro assays and mouse peripheral blood micronucleus assay, but is in mouse liver micronucleus assay. Environ Mol Mutagen 3 2 (3 ) 2 69-2 80, 1998... 

Methyl acrylate was not found to be mutagenic in the Salmonella assay, but it increased chromosomal aberrations in vitro and tested positive in the micronucleus assay in mice. ... 

MEKP was not mutagenic in bacterial assays, but it did induce sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells it was also negative in the in vivo mouse micronucleus assay. ... 

Mutagenesis Human peripheral blood lymphocytes were exposed to zalcitabine, and at 1.5 mcg/mL or more, dose-related increases in chromosomal aberrations were seen. Oral doses of zalcitabine at 2500 and 4500 mg/kg were clastogenic in the mouse micronucleus assay. 

In vitro mammalian cell assay chromosome aberrations or tk mutations in mouse lymphoma cells 10 mM In vitro mammalian cell assay chromosome aberrations or tk mutations in mouse lymphoma cells or in vitro micronucleus assay 1 mM or 0.5 mg/ml top concentration No in vitro mammalian assay... 

Diaz, D., Scott, A., Carmichael, P Shi, W. and Costales, C. (2007) An assessment of the performance of an automated scoring system (Cellomics) for the in vitro micronucleus assay in CHO-Kl cells. Mutation Research, 630, 1-13. 

Bryce, S.M., Avlasevich, S.L., Bemis, J.C., Lukamowicz, M Elhajouji, A., Van Goethem, F., De Boeck, M Beerens, D. et al. (2008) Interlaboratory evaluation of a flow cytometric, high content in vitro micronucleus assay. Mutation Research, 650, 181-195. 

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