In vitro and in vivo incorporation of 63Ni[II] into lung and liver subcellular fractions of Balb/C mice.

The binding of nickel to proteins in lung and in liver was investigated by analysis of 63Ni[II] incorporation into the nuclear, mitochondrial, microsomal and soluble fractions. Three different procedures were performed: (i) in vitro incorporation, (ii) a time course study of in vivo incorporation where the animals were sacrificed after 30 min, 1, 2 and 4 h after a single i.p. injection of 63NiCl2, (iii) in vivo incorporation after 7 successive i.p. injections of 63NiCl2 every 24 h and the animals were sacrificed 24 h after the last injection. In all cellular fractions (except the nuclear fractions) we could observe several nickel-binding proteins regardless of the type of incorporation performed. Most of these proteins were revealed after in vitro as well as in vivo incorporation, some of them, however, were labelled only after in vitro incorporation, others only after in vivo incorporation. Some proteins can only be revealed after successive injections. In addition, the 63Ni-labelled proteins are not all the same at the beginning of the incorporation (30 min) as after longer periods (1 and 2 h). The lung fractions (especially the mitochondrial fraction) were always more highly labelled than the liver fractions. These biochemical investigations not only confirm that the lung is a target organ for nickel-retention, but also demonstrate that Ni is preferentially bound to its mitochondrial and microsomal fractions. It is shown here that several cellular proteins are implicated in the transport and the metabolism of nickel in the cell.