Characterization of mouse cell lines resistant to nickel(II) ions.

BALB/c-3T3 cells have been isolated that are resistant to NiCl2. The degree of resistance is directly dependent upon the NiCl2 exposure concentration and ranges from 6- to 11-fold. Resistance to NiCl2 does not appear to be due to alterations in cellular uptake, since the entry of Ni(II) into wild-type or resistant cells was similar. Resistance does not appear to be due to alterations in metallothionein expression. Resistant cells have a high incidence of heterochromatic abnormalities involving fusions at the centromeres as determined by C-banding and in situ hybridization utilizing a cloned mouse satellite DNA probe. Cells retain nickel resistance for many generations in the absence or presence of NiCl2 selection; however, with time in the absence of NiCl2, the level of resistance decreases. This loss of resistance is associated with a decreased number of centromeric fusions. These results indicate that nickel resistance is involved with changes in heterochromatin and suggest that this effect of nickel on heterochromatin may be important as an early step in nickel carcinogenesis.