A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins

Kirkland, David; Reeve, Lesley; Gatehouse, D.; Vanparys, Philippe

doi:10.1016/j.mrgentox.2010.12.015

Cited by 197 publications

(105 citation statements)

References 1,178 publications

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“…1 It is also reported to be an essential test within the current battery of assays required for evaluation of genotoxicity. 40 To date, there have been a few reports on the mutagenicity of nanoparticles such as aluminum oxide, cobalt oxide, titanium oxide, and zinc oxide based on the bacterial mutation assay. Hence, we performed this assay using strains of S. typhimurium TA98, TA100, TA1535, and TA1537, and E. coli WP2uvrA, with and without metabolic activation by S9 mixture.…”

Section: Discussionmentioning

confidence: 99%

Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo tests

Kwon

Kim

Lee

et al. 2014

IJN

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Background Silica dioxide (SiO 2 ) has been used in various industrial products, including paints and coatings, plastics, synthetic rubbers, and adhesives. Several studies have investigated the genotoxic effects of SiO 2 ; however, the results remain controversial due to variations in the evaluation methods applied in determining its physicochemical properties. Thus, well characterized chemicals and standardized methods are needed for better assessment of the genotoxicity of nanoparticles. Methods The genotoxicity of SiO 2 was evaluated using two types of well characterized SiO 2 , ie, 20 nm (−) charge (SiO EN20(−) 2) and 100 nm (−) charge (SiO EN100(−) 2). Four end point genotoxicity tests, ie, the bacterial mutation assay, in vitro chromosomal aberration test, in vivo comet assay, and in vivo micronucleus test, were conducted following the test guidelines of the Organization for Economic Cooperation and Development (OECD) with application of Good Laboratory Practice. Results No statistically significant differences were found in the bacterial mutation assay, in vitro chromosomal aberration test, in vivo comet assay, and in vivo micronucleus test when tested for induction of genotoxicity in both two types of SiO 2 nanoparticles. Conclusion These results suggest that SiO 2 nanoparticles, in particular SiO 2 EN20(−) and SiO 2 EN100(−) , are not genotoxic in both in vitro and in vivo systems under OECD guidelines. Further, the results were generated in accordance with OECD test guidelines, and Good Laboratory Practice application; it can be accepted as reliable information regarding SiO 2 -induced genotoxicity.

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Section: Discussionmentioning

confidence: 99%

Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo tests

Kwon

Kim

Lee

et al. 2014

IJN

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“…Li et al [24] also reported that human lymphoblastoid cells exposed to 5 nm Ag-NPs showed a dose dependent increase in MN frequency. Furthermore, Foldbjerg et al [25] reported that DNA damage was detected as an increase in bulky DNA adducts by 32P post-labeling in human alveolar cells exposed to 120-150 nm Ag-NPs. On the contrary, no significant genotoxic responses were observed in an Ames test (5 nm) [26], a mouse lymphoma assay (< 100 nm) [27] and an in vivo MN assay (60 nm) [28].…”

Section: Resultsmentioning

confidence: 99%

Anti Genotoxic Effect of TiO2 Nanoparticle Biosynthesized from Sargassum polycystum - a Marine Macroalgae

Ali¹

2017

JNMR

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Nanotechnology is the application of science and technology to control matter at the molecular level, which is also referred to as the ability for designing, production, characterization and application to structures, devices and systems by controlling shape and size at the nanometer scale The present study was an attempt to investigate antigenotoxic effect of TiO 2 nanoparticle biosynthesized from Sargassum polycystum Our work aimed at conducting Genotoxicity studies for the screening of Mutagenicity using Ames test and to prove this as a antigenotoxicant. The mutagens (positive controls) treated without metabolic activation system showed a 3 fold increase of average revertant colonies per plate when compared with that of concurrent vehicle controls, thus exhibiting the ability to identify the mutagen by the tester strains. The mutagenicity assay was performed with three dose levels (0.312, 1.25, and 5.0 mg/ml) in the absence of metabolic activation system. Inhibition of background growth of non-revertant bacteria was not found at any of the three dose levels. Furthermore works are to be carried out in future to find the exact mechanism of its genoprotective nature.

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“…It would appear that a strategy of three tests is not better than two tests although it is generally felt to be "safer". In a recent analysis of an existing database of rodent carcinogens and a new database of in vivo genotoxins, together covering over 950 substances, Kirkland et al (2011) confirmed that data from the gene mutation test in bacteria and the in vitro micronucleus test allowed the detection of all the relevant in vivo carcinogens and in vivo genotoxins for which data exist in these databases. Consequently, it would appear that the starting point should be a combination of two in vitro tests.…”

Section: Combinations Of In Vitro Genotoxicity Testsmentioning

confidence: 86%

Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment

2011

EFS2

285

136

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The Scientific Committee reviewed the current state-of-the-science on genotoxicity testing and provided a commentary and recommendations on genotoxicity testing strategies. A step-wise approach is recommended for the generation and evaluation of data on genotoxic potential, beginning with a basic battery of in vitro tests, comprising a bacterial reverse mutation assay and an in vitro micronucleus assay. Consideration should be given to whether specific features of the test substance might require substitution of one or more of the recommended in vitro tests by other in vitro or in vivo tests in the basic battery. In the event of negative in vitro results, it can be concluded that the substance has no genotoxic potential. In case of inconclusive, contradictory or equivocal results, it may be appropriate to conduct further testing in vitro. In case of positive in vitro results, review of the available relevant data on the test substance and, where necessary, an appropriate in vivo study to assess whether the genotoxic potential observed in vitro is expressed in vivo is recommended. Suitable in vivo tests are the mammalian erythrocyte micronucleus test, transgenic rodent assay, and Comet assay. The approach to in vivo testing should be step-wise. If the first in vivo test is positive, no further testing is necessary and the substance should be considered as an in vivo genotoxin. If the test is negative, it may be possible to conclude that the substance is not an in vivo genotoxin. However, in some cases, a second in vivo test may be necessary (e.g. if the first test is negative but more than one endpoint in the in vitro tests are positive, an in vivo test on a second endpoint may be necessary). The combination of assessing different endpoints in different tissues in the same animal in vivo should also be considered.

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A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins

Cited by 197 publications

References 1,178 publications

Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo tests

Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo tests

Anti Genotoxic Effect of TiO2 Nanoparticle Biosynthesized from Sargassum polycystum - a Marine Macroalgae

Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment

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