Nickel-bound chromatin, nucleic acids, and nuclear proteins from kidney and liver of rats treated with nickel carbonate in vivo

The in vivo binding of nickel to chromatin, nucleic acids, and nuclear proteins from rat kidney and liver was investigated. Evidence is presented for the direct interaction of nickel with chromatin from rat tissues following i.p. injection of nickel carbonate. A gentle DNA isolation procedure was developed and used to isolate nickel-bound whole chromatin, DNA + histone octamer complex (polynucleosomes), and deproteinized DNA from kidney and liver nuclei. A similar procedure was developed for isolating nickel-bound RNA from the cytoplasm. The level of nickel bound to whole chromatin from kidney was higher than that from liver, and these levels could be related to the nuclear concentration of nickel. Much higher levels of nickel were bound to the DNA + histone octamer complex and purified, deproteinized DNA from kidney as compared to liver. Substantial levels of nickel were bound to nonhistone proteins and/or chromatin-associated RNA from kidney and liver nuclei. Nickel was also associated with histone octamer proteins from kidney; however, little or no nickel was associated with histone octamer proteins from liver. 63Ni binding to nuclear proteins in rats given injections of 63Ni(II) was investigated by using two different gel electrophoretic systems. Electrophoretic conditions in both systems were found to remove protein-bound 63Ni. These results are discussed relative to the molecular mechanism of nickel carcinogenesis.