Targets and mechanisms of chemically induced aneuploidy. part 1 of the report of the 2017 iwgt workgroup on assessing the risk of aneugens for carcinogenesis and hereditary diseases

Publication date: Available online 2 March 2019Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Anthony M. Lynch, David Eastmond, Azeddine Elhajouji, Roland Froetschl, Micheline Kirsch-Volders, Francesco Marchetti, Kenichi Masumura, Francesca Pacchierotti, Maik Schuler, David TweatsAbstractAn aneuploidy workgroup was established as part of the 7th International Workshops on Genotoxicity Testing. The workgroup conducted a review of the scientific literature on the biological mechanisms of aneuploidy in mammalian cells and methods used to detect chemical aneugens. In addition, the current regulatory framework was discussed, with the objective to arrive at consensus statements on the ramifications of exposure to chemical aneugens for human health risk assessment. As part of these efforts, the workgroup explored the use of adverse outcome pathways (AOPs) to document mechanisms of chemically induced aneuploidy in mammalian somatic cells. The group worked on two molecular initiating events (MIEs), tubulin binding and binding to the catalytic domain of aurora kinase B, which result in several adverse outcomes, including aneuploidy. The workgroup agreed that the AOP framework provides a useful approach to link evidence for MIEs with aneuploidy on a cellular level. The evidence linking chemically induced aneuploidy with carcinogenicity and hereditary disease was also reviewed and is presented in two companion papers. In addition, the group came to t...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research