Potential thresholds for genotoxic effects by micronucleus scoring

Elhajouji, Azeddine; Lukamowicz, Magdalena; Cammerer, Zoryana; Kirsch‐Volders, Micheline

doi:10.1093/mutage/geq089

Cited by 83 publications

(58 citation statements)

References 45 publications

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“…In the same way, the number of mitoses remained constant whatever the concentration of quinolones (NA) and fluoroquinolones (ENR and CIP) tested. In the last decades, several studies suggested the concept of thresholds in genotoxicity (Lynch et al, 2003;Elhajouji et al, 2010). The MN test contributed to a large extent in understanding the dose-response relationship for aneugens and clastogens.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test

Khadra¹,

Pinelli²,

Lacroix³

et al. 2012

Ecotoxicology and Environmental Safety

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, et al.. Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test. Ecotoxicology and Environmental Safety, Elsevier, 2012, 76, pp.187-192. <10.1016/j.ecoenv.2011 a b s t r a c tThe genotoxicity of quinolone and fluroquinolones was assessed using the micronucleus (MN) test on Vicia faba roots by direct contact exposure to a solid matrix. Plants were exposed to quinolones (nalidixic acid) and fluoroquinolones (ciprofloxacin and enrofloxacin) alone or mixed with artificially contaminated soils. Four different concentrations of each of these antibiotics were tested (0.01, 0.1, 1 and 10 mg/Kg) for nalidixic acid and (0.005, 0.05, 0.5 and 5 mg/Kg) for ciprofloxacin and enrofloxacin. These antibiotics were also used in mixture. Exposure of Vicia faba plants to each antibiotic at the highest two concentrations showed significant MN induction. The lowest two concentrations had no significant genotoxic effect. The mixture of the three compounds induced a significant MN induction whatever the mixture tested, from 0.02 to 20 mg/Kg. The results indicated that a similar genotoxic effect was obtained with the mixture at 0.2 mg/Kg in comparison with each molecule alone at 5-10 mg/Kg. Data revealed a clear synergism of these molecules on Vicia faba genotoxicity.

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Section: Discussionmentioning

confidence: 99%

Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test

Khadra¹,

Pinelli²,

Lacroix³

et al. 2012

Ecotoxicology and Environmental Safety

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“…When used for therapy the balance between benefits/potential adverse effects has to be considered. In this case, the practical question is essentially determining the lowest effective dose, which is ruled in general by thresholded dose-response curves [34,35]. Our concern is which undesired consequences of responses to NMs may result from binding to tubulins.…”

Section: Discussionmentioning

confidence: 99%

Induction of chromosome malsegregation by nanomaterials

Gonzalez

Decordier

Kirsch‐Volders

2010

Biochemical Society Transactions

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NMs (nanomaterials), defined as materials with at least one dimension smaller than 100 nm, are able to induce genotoxic effects. One of the hypotheses of the mode-of-action in which they exert their genotoxic potential is to mechanically interfere with subcellular structures, in particular the microtubules. In the present paper, we review studies exploring interactions between NMs and tubulin; therefore a PubMed literature search was performed. From this search 12 studies, applying both acellular and cellular assays, were retrieved and are summarized according to endpoint and particle type. These studies show that there are interactions between different types of NMs and tubulins in both acellular and cellular systems. For several types of NMs, the multi-walled carbon nanotubes, amorphous SiO(2), TiO(2) and CoCr, an induction of aneuploidy was observed in vitro. There is, therefore, a critical need to assess the capacity of NMs to interfere with the cytoskeleton, and in particular the tubulins. This might require definition of relevant dosimetry, adaptations of some testing protocols, possibly development of new methodologies and studies on a larger size-range of NMs.

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“…For example, some non-DNA-reactive mechanisms are expected to have a threshold of exposure below which there is no biological effect (e.g. [3][4][5][6][7]). When evidence supporting the mechanism is sufficient, a relatively small margin of exposure below a minimal effect level may be acceptable.…”

Section: Extrapolation Below the Podmentioning

confidence: 99%

IWGT report on quantitative approaches to genotoxicity risk assessment II. Use of point-of-departure (PoD) metrics in defining acceptable exposure limits and assessing human risk

MacGregor¹,

Frötschl

White

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

112

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This is the second of two reports from the International Workshops on Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized the discussions and recommendations of the QWG related to the need for quantitative dose-response analysis of genetic toxicology data, the existence and appropriate evaluation of threshold responses, and methods to analyze exposure-response relationships and derive points of departure (PoDs) from which acceptable exposure levels could be determined. This report summarizes the QWG discussions and recommendations regarding appropriate approaches to evaluate exposure-related risks of genotoxic damage, including extrapolation below identified PoDs and across test systems and species. Recommendations include the selection of appropriate genetic endpoints and target tissues, uncertainty factors and extrapolation methods to be considered, the importance and use of information on mode of action, toxicokinetics, metabolism, and exposure biomarkers when using quantitative exposure-response data to determine acceptable exposure levels in human populations or to assess the risk associated with known or anticipated exposures. The empirical relationship between genetic damage (mutation and chromosomal aberration) and cancer in animal models was also examined. It was concluded that there is a general correlation between cancer induction and mutagenic and/or clastogenic damage for agents thought to act via a genotoxic mechanism, but that the correlation is limited due to an inadequate number of cases in which mutation and cancer can be compared at a sufficient number of doses in the same target tissues of the same species and strain exposed under directly comparable routes and experimental protocols.

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Potential thresholds for genotoxic effects by micronucleus scoring

Cited by 83 publications

References 45 publications

Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test

Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test

Induction of chromosome malsegregation by nanomaterials

IWGT report on quantitative approaches to genotoxicity risk assessment II. Use of point-of-departure (PoD) metrics in defining acceptable exposure limits and assessing human risk

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