Ni(II) induced changes in cell cycle duration and sister-chromatid exchanges in cultured human lymphocytes

Investigations from our laboratory and others have shown that Ni(II) treatments of cultured human lymphocytes produced a relatively small but significant increase in SCE frequency. Based on the known effects of Ni(II) on DNA replication, we evaluated whether Ni(II) produced a cell cycle delay in lymphocytes. Human lymphocytes of three normal subjects were exposed to 5, 10, and 25 microM of NiSO4 in culture medium and scored for the percent of metaphases in the first (M1), second (M2), and third (M3) cell cycle for harvest times spaced every 4 h from 36 to 72 h after culture initiation. Cell cycle duration was studied using Tice's BISACK method with certain modifications. All three doses of NiSO4 caused a delay of nearly 1.5 h in the initiation of cell division, but only 25 microM NiSO4 caused a lengthening in the cell cycle time of nearly 4 h for completion of the first cycle. Only at the highest dose of Ni(II) was there a significant increase in the SCE frequency compared to the control. When the proliferation rate index (PRI) was examined, the effect of 5 or 10 microM Ni(II) was negligible while the 25 microM concentration caused a suppression in the proliferation rate. The effect of Ni(II) on the cell cycle was much more pronounced than on the PRI. A significant increase in SCE frequency was observed only for the concentration of Ni(II) that caused a pronounced cell cycle delay, a result that is consistent with prior studies showing higher SCE responses for chemical treatments that lengthen the cell cycle.