Pathway of nickel uptake influences its interaction with heterochromatic DNA.

Exposure of intact Chinese hamster ovary cells to water-soluble NiCl2 and to particulate crystalline NiS induced a concentration-dependent incidence of chromosomal aberrations which included gaps, breaks, and exchanges. Exposure of cells to crystalline NiS particles caused a high incidence of chromatid exchanges and dicentrics and produced what appears to be an effect on the condensation state of the heterochromatic long arm of the X chromosome. Treatment of cells with NiCl2 did not cause any significant effect on the long arm of the X chromosome, and there was a much lower incidence of the dicentric type of chromosomal aberrations compared to NiS. To examine whether the fragmentation/decondensation of the long arm of the X chromosome produced by crystalline NiS particles was due to a phagocytic pathway of uptake of NiS particles, cells were treated with NiCl2-albumin complexes that had been encapsulated in liposomes. Although treatment of cells with NiCl2-albumin complexes yielded higher intracellular nickel levels than were obtained by treatment of cells with NiCl2, at comparable intracellular levels fragmentation/decondensation of the heterochromatic long arm of the X chromosome was observed when nickel (II) was delivered by way of a liposome but not when cells were treated with unencapsulated NiCl2. Ionic nickel alone irrespective of its delivery mechanism exhibited some preference for heterochromatin, since there was a higher incidence of aberrations observed in the heterochromatic centromeric region of chromosomes. These observations suggest that the pathway of delivery of Ni2+ from NiS particles may be responsible for a preferential interaction of this metal with heterochromatin leading to an effect on the condensation state/fragmentation of the heterochromatic long arm of the X chromosome.