Cell Cycle Arrest, Apoptosis and P53 Expression in Nickel(Ii) Acetate-Treated Chinese Hamster Ovary Cells

Nickel(II) compounds are known human and animal carcinogens, In this study, the effects of nickel(II) acetate on cell cycle, apoptosis and p53 expression were investigated in order to unveil the elements of early cellular responses to the metal, Chinese hamster ovary (CHO) cells were grown for 72 h in Ham's F-12 medium containing 0, 40, 80, 160, 240, 320, 480 or 640 mu M nickel(LI) acetate, DNA fragmentation, representative of apoptosis, was examined by agarose gel electrophoresis, The distribution of cells among various phases of cell cycle was determined by DNA flow cytometry, Expression of p53 protein was measured by the Western blotting technique. DNA fragmentation was detectable in cells treated with greater than or equal to 160 mu M nickel(II) and its intensity increased with increasing nickel(II) concentration. The proportion of cells at S phase declined in a nickel(II) concentration-dependent manner. The decline was accompanied by an increase of cell proportion in G(2)/M phase and the increase became statistically significant in cells exposed to at least 480 mu M nickel(II). Expression of p53 protein was not different from that in the control among samples treated with less than or equal to 480 mu M nickel(II), However, an extra fraction that migrated close to the p53 protein fraction was detected in cells treated with 640 mu M nickel(II). Our findings suggest that nickel(II) modulates cellular response through effecters involved in both G(2)/M arrest and apoptosis regulatory pathways, The proportion of cells arrested at G(2)/M phase or undergoing apoptosis depends directly on nickel(II) concentration. High concentration of nickel(II) appears to up-regulate protein(s) other than the common form of p53 protein. [References: 23]

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