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) t reatments of cultured human lymphocytes produced a relatively small bu t significant increase in SCE frequency. Based on the known effects of Ni(II) on DNA replication, we evaluated whether Ni(II) produced a cel l cycle delay in lymphocytes. Human lymphocytes of three normal subjec ts were exposed to 5, 10, and 25 mu M of NiSO4 in culture medium and s cored for the percent of metaphases in the first (M1), second (M2), an d 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 T ice's BISACK method with certain modifications. All three doses of NiS O4 caused a delay of nearly 1.5 h in the initiation of cell division, but only 25 mu M NiSO4 cused a lengthening in the cell cycle time of n early 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 compar ed to the control. When the proliferation rate index (PRI) was examine d, the effect of 5 or 10 mu M Ni(II) was negligible while the 25 mu M concentration caused a suppression in the proliferation rate. The effe ct of Ni(II) on the cell cycle was much more pronounced than on the PR I. A significant increase in SCE frequency was observed only for the c oncentration of Ni(II) that caused a pronounced cell cycle delay, a re sult that is consistent with prior studies showing higher SCE response s for chemical treatments that lengthen the cell cycle.