Toxic metals produce an S-phase-specific cell cycle block.

In order of decreasing potency, CdCl2 greater than HgCl2 greater than CoCl2 greater than CuSO4 greater than NiCl2 greater than ZnCl2 and PbSO4 slowed cell growth at concentrations ranging from 1 microM to 60 microM. Flow cytometry analysis of cell cycle position indicated that cell growth was selectively blocked in S phase by these concentrations. Water insoluble metals such as As, Ni, crystalline Ni3S2, crystalline NiS, crystalline Ni3Se2 and NiO also resulted in an S phase blockage of cells at concentrations of 1 to 10 micrograms/ml. The crystalline nickel sulfide and selenide compounds as well as As metal were the most potent of these. At higher concentrations blockage of cells in mitosis was also evident with a number of the water insoluble metal compounds. The potency of the metal compounds in blocking cells in S phase was related to their chemical reactivity and their uptake into cells. The S phase specific blockage produced by the metals examined was consistent with their genotoxic or carcinogenic activity since such activity indicated a selective interaction with DNA metabolism.