Chemically induced aneuploidy in germ cells. part ii of the report of the 2017 iwgt workgroup on assessing the risk of aneugens for carcinogenesis and hereditary diseases

Publication date: Available online 20 March 2019Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Francesca Pacchierotti, Kenichi Masumura, David Eastmond, Azeddine Elhajouji, Roland Froetschl, Micheline Kirsch-Volders, Anthony Lynch, Maik Schuler, David Tweats, Francesco MarchettiAbstractAs part of the 7th International Workshops on Genotoxicity Testing held in Tokyo, Japan in November 2017, a workgroup of experts reviewed and assessed the risk of aneugens for human health. The present manuscript is one of three manuscripts from the workgroup and reports on the unanimous consensus reached on the evidence for aneugens affecting germ cells, their mechanisms of action and role in hereditary diseases. There are 24 chemicals with strong or sufficient evidence for germ cell aneugenicity providing robust support for the ability of chemicals to induce germ cell aneuploidy. Interference with microtubule dynamics or inhibition of topoisomerase II function are clear characteristics of germ cell aneugens. Although there are mechanisms of chromosome segregation that are unique to germ cells, there is currently no evidence for germ cell-specific aneugens. However, the available data are heavily skewed toward chemicals that are aneugenic in somatic cells. Development of high-throughput screening assays in suitable animal models for exploring additional targets for aneuploidy induction, such as meiosis-specific proteins, and to prioritize chemicals for the...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research