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The lymphocyte cytokinesis block micronucleus test in human populations occupationally exposed to vinyl chloride Vrije Universiteit Brussel

Claudia Bolognesi, Marco Bruzzone, Marcello Ceppi, Micheline Volders

Vinyl chloride (VC) is widely used in industry in the production of polyvinyl chloride (PVC), which is used to manufacture a large variety of materials. VC was classified as a known (Group 1) human carcinogen by IARC on the basis of increased risk for liver angiosarcoma and hepatocellular cancer, and the carcinogenicity of VC was shown to be mediated by a genotoxic mechanism. Following inhalation, the compound is rapidly absorbed and ...

Flow cytometry peripheral blood micronucleus test in vivo: Determination of potential thresholds for aneuploidy induced by spindle poisons Vrije Universiteit Brussel

Zoryana Cammerer, Martin M Schumacher, Micheline Volders, Willi Suter, Azddine Elhajouji
Non-DNA binding genotoxins (e.g., aneugens), unlike DNA-binding genotoxins, are theoretically expected to show thresholded concentration-effect response curves. This is a major issue in genetic toxicology testing because the identification of thresholds in vivo can provide a safety margin for exposure to a particular compound. In the current study we measured micronucleus induction by flow cytometry to determine the dose-response curves for ...

The Buccal Cell Micronucleus Test for Monitoring Human Exposure to Genotoxic Agents Vrije Universiteit Brussel

E. Zeiger, N. Holland, Micheline Volders, S. Bonassi, C. Bolognesi, S Knasmueller, M. Fenech
The Buccal Micronucleus Cytome (BMCyt) assay is a minimally invasive method for studying DNA damage, chromosomal instability, cell death and the regenerative potential of human buccal mucosal tissue. This method is increasingly used in molecular epidemiological studies for investigating the impact of nutrition, lifestyle factors, genotoxin exposure and genotype on DNA damage, chromosome malsegregation and cell death. The biomarkers measured in ...

New QSAR models to predict chromosome damaging potential based on the in vivo micronucleus test Universiteit Antwerpen Vrije Universiteit Brussel

Melissa Van Bossuyt, Giuseppa Raitano, Masamitsu Honma, Els Van Hoeck, Tamara Vanhaecke, Vera Rogiers, Birgit Mertens, Emilio Benfenati
A large number of computer-based prediction methods to determine the potential of chemicals to induce mutations at the gene level has been developed over the last decades. Conversely, only few such methods are currently available to predict potential structural and numerical chromosome aberrations. Even fewer of these are based on the preferred testing method for this endpoint, i.e. the micronucleus test. For the present work, in vivo ...

Fluorescence in situ hybridization (FISH) technique for the micronucleus test. Vrije Universiteit Brussel

Ilse Decordier, Micheline Volders
In recent years, cytogenetics in combination with molecular methods has made rapid progress, resulting in new molecular cytogenetic methodologies such as fluorescence in situ hybridization (FISH). FISH is a molecular cytogenetic technique used for the detection of specific chromosomal rearrangements and applicable to many different specimen types. It uses fluorescently labeled DNA probes complementary to regions of individual chromosomes. These ...

Micronucleus frequency in Danish schoolchildren and their mothers from the DEMOCOPHES population Vrije Universiteit Brussel

Thit A Mørck, Kim Vande Loock, Maria Bech Poulsen, Volkert D Siersma, Jeanette K S Nielsen, Ole Hertel, Micheline Volders, Lisbeth E. Knudsen

Micronucleus (MN) frequency is a biomarker for early genetic effects which is often used in human biomonitoring studies. Increased frequency of micronuclei has been associated with high levels of traffic exposure. Further high MN frequency was found predictive for cancer development in several studies of adults. In the present study, the MN frequency in blood samples from the Danish participants of the European pilot project DEMOCOPHES was ...

Validity of the Lymphocyte Cytokinesis-Block Micronucleus Assay (L-CBMN) as biomarker for human exposure to chemicals with different modes of action Vrije Universiteit Brussel

Micheline Volders, Michael Fenech, Claudia Bolognesi

Recently fourteen systematic reviews applying the same selection and evaluation criteria analyzed the induction of micronuclei in lymphocytes as biomarker for DNA damage induced by human exposure to a given chemical or chemical mixture. The results obtained in the individual reviews were summarized to evaluate the validity of the Cytokinesis-Block-Micronucleus assay in lymphocytes (L-CBMN) and propose recommendations for its use in ...

The cytokinesis-block micronucleus assay on human isolated fresh and cryopreserved peripheral blood mononuclear cells Universiteit Gent

Simon Sioen, Karlien Cloet, Anne Vral, Ans Baeyens
The cytokinesis-block micronucleus (CBMN) assay is a standardized method used for genotoxicity studies. Conventional whole blood cultures (WBC) are often used for this assay, although the assay can also be performed on isolated peripheral blood mononuclear cell (PBMC) cultures. However, the standardization of a protocol for the PBMC CBMN assay has not been investigated extensively. The aim of this study was to optimize a reliable CBMN assay ...

Impact of experimental design factors on the potency of genotoxicants in in vitro tests Vrije Universiteit Brussel

Julie Sanders, Anouck Thienpont, Roel Anthonissen, Tamara Vanhaecke, Birgit Mertens

Previous studies have shown that differences in experimental design factors may alter the potency of genotoxic compounds in in vitro genotoxicity tests. Most of these studies used traditional statistical methods based on the lowest observed genotoxic effect levels, whereas more appropriate methods, such as the benchmark dose (BMD) approach, are now available to compare genotoxic potencies under different test conditions. We therefore ...

Micronuclei as biomarkers of DNA damage, aneuploidy, inducers of chromosomal hypermutation and as sources of pro-inflammatory DNA in humans Vrije Universiteit Brussel

Michael Fenech, Siegfried Knasmueller, Claudia Bolognesi, Nina Holland, Stefano Bonassi, Micheline Volders

Micronuclei (MNi) are among the most widely studied biomarkers of DNA damage and chromosomal instability in humans. They originate from chromosome fragments or intact chromosomes that are not included in daughter nuclei during mitosis. The main reasons for their formation are a lack of functional centromere in the chromosome fragments or whole chromosomes or defects in one or more of the proteins of the mitotic system that, consequently, ...