Long-term exposure to submicromolar arsenite induces bypass of the spindle assembly checkpoint in mammalian cells

Mitosis is regulated by checkpoints that delay mitotic progression when chromosome segregation errors occur. Inaccuracy in checkpoint processes can lead to chromosome instability both in number and structure (CIN). Arsenic is reported to induce CIN by perturbing mitotic spindles and checkpoints, however, its carcinogenic mechanisms are poorly understood. We previously studied the long-term progression of chromosomal instability in V79 cells treated acutely with arsenite (10 M, 24 hr) followed by growth in arsenic-free medium for 120 cell generations, and found time-dependent increase of aneuploid cells. Here, we treated V79-derived G12 cells with sub-lethal doses (0.1-1.0 µM) of arsenite f…