Centrosome amplification and multinuclear phenotypes are Induced by hydrogen peroxide

Multinucleated cells resulted from mitosis defect have been noted in pathophysiological states of the cells such as inflammation, senescence and cancer. Since oxidative stress has been known to correlate with these pathophysiological conditions, we tested the effect of H2O2 on the cell cycle progression and formation of multinucleated cells. H2O2 induced a significant delay in cell cycle progression in Chang liver cells. Interestingly, H2O2 actively induced hyperamplification of centrosomes (> or =3) and multipolar spindle formation during mitosis and subsequently increased the generation of multinucleated cells. A significant increase of the phospho-ERK level was observed upon H2O2 treatment but PD98059, an MEK1/2 inhibitor, didn't reduce the frequency of cells with hyperamplified centrosomes. On the other hand, treatment of either H2O2 or adriamycin increased intracellular ROS levels and multinucleated cells, which were significantly suppressed by antioxidants, N-acetylcysteine and PDTC. Thus, our results suggest that oxidative stress can trigger centrosome hyperamplification and multinucleated cell formation, which may promote pathophysiological progression.

Spindle damaging effect of salbutamol sulphate on bone marrow cells of mice.

In vivo assessment and identification of aneuploidy are important phases of genotoxicity evaluation. Considerable effort has been devoted to assess the utility of the existing bioassays and to develop simpler techniques for identifying environmental aneugens. Salbutamol sulphate--an antiasthmatic drug was tested for its spindle damaging effects in bone marrow cells of mice using an in vivo technique, for the evaluation of mitotic index, C-mitotic effects, anaphase reduction and hyperdiploidy. Doses of 0.12, 0.24, 1.2, 2.4, mg/kg body weight were dissolved in bidistilled water and administered intraperitoneally to the mice. Colchicine was taken as positive control for its known aneuploidy-inducing effects. The drug showed positive C-mitotic effects accompanied with increases of mitotic index and decreased frequencies of anaphase in higher doses. Significant levels of hypodiploidy also noted at higher doses. The preliminary results indicated that Salbutamol is capable of inducing C-mitotic effects in mouse bone marrow cells, which is suggestive of possible induction of aneuploidy.