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.
D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D025063:Chromosome Disorders; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D005260:Female; D006570:Heterochromatin / Q000187:drug effects* / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D009532:Nickel; D010053:Ovary / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects
D006570:Heterochromatin; D008081:Liposomes; D012709:Serum Albumin; C022838:nickel chloride; D009532:Nickel; D004247:DNA; C017558:nickel sulfide