Abstract
Environmental pollution is a big challenge for human survival. Arsenic compounds are well-known biohazard, the exposure of which is closely linked to onsets of various human diseases, particularly cancers. Upon chronically exposing to arsenic compounds, genomic integrity is often disrupted, leading to tumor development. However, the underlying mechanisms by which chronic, low dose arsenic exposure targets genetic stability to initiate carcinogenesis still remain not fully understood. In this study, human lung epithelial BEAS-2B cells and keratinocytes were treated with 0.5 μM of sodium arsenite for one month (designated as BEAS-2B-SA cells or keratinocytes-SA), and its effect on cell cycle responses was analyzed. After being arrested in mitotic phase of the cell cycle by nocodazole treatment, BEAS-2B-SA cells or keratinocytes-SA were delayed to enter next cytokinesis. The lagging exit of the cells from mitosis was accompanied by a sustained Plk1 phosphorylation, which led to a persistent activation of the mitotic regulators BubR1 and Cdc27. As the result, cyclin B1 (clnB1) degradation was attenuated. BEAS-2B-SA cells or keratinocytes-SA also expressed a constitutively active Akt. The cytogenetic analysis showed an increased numbers of aneuploidy in these cells. The suppression of Akt reversed the aberrant expressions of the mitotic regulators, delay of mitotic exit as well as chromosomal aberrations. Our findings suggest that a long-term exposure to low dose sodium arsenite aberrantly retains the catenation of mitosis, which facilitates establishing genetic instability and predisposes the cells to tumorigenesis.