Chemically induced aneuploidy in mammalian cells in culture

Our objectives were to assess whether there exist useful aneuploidy tests in vitro, to identify chemicals that showed potential for mitotic aneuploidy induction, and to recommend some features of suitable protocols for such testing. From over 100 papers we selected 24 for review. The acceptable studies examined hyperdiploidy at metaphase, had concurrent negative controls with low background rates of hyperdiploidy, used a fixation time sufficient for cells to complete more than one cell cycle after treatment and had multiple dose levels with at least 100 cells scored per point. We judged that 12 compounds were positive, 7 inconclusive, and 4 negative with the reservation that 2 of the 4 compounds had not been tested up to toxic doses. Many of the positive compounds are also known to cause structural chromosome aberrations. We separately reviewed qualitative reports of 'C-mitotic' effects, anaphase lagging, multipolar mitoses, or altered DNA content, since these effects may sometimes by associated with aneuploidy induction. No well-validated in vitro aneuploidy assay exists, and much research is required to develop tests, perhaps using chromosome counts, DNA content, or effects on cell organelles necessary for mitosis. In test protocol development we should carefully consider choice of cell sample size, use of in vitro metabolic activation systems, and selection of doses, especially with regard to the problem of whether cytotoxic concentrations should be used.