Effects of nickel sulfate on growth and differentiation of normal human bronchial epithelial cells.

Epidemiological studies have shown that inhalation of nickel compounds enhances the risk of human respiratory cancer. Cultures of normal human bronchial epithelial cells were continuously exposed to a dose (5-20 micrograms/ml) of NiSO4 that reduced their colony forming efficiency by 30-80%. After 40 days of incubation, the cultures consisted of large, squamous cells; mitotic cells were not observed. The cells were then maintained in medium without NiSO4. After 40-75 total days of incubation, colonies of mitotic cells appeared at a rate of 1 colony per 100 000 cells originally at risk; no colonies appeared in control cultures or in cultures exposed to less than 5 micrograms NiSO4/ml for 90 days. Twelve NiSO4-altered cell cultures isolated from five experiments have been expanded into mass cultures. Most of the cell lines have an increased population doubling potential (greater than 50 divisions). Some exhibit aberrations in the squamous (terminal) differentiation process whereas others have lost the requirement for epidermal growth factor for clonal growth. Aneuploidy and marker chromosomes have also been noted. However, none of these NiSO4-altered cell cultures are anchorage independent nor do they produce tumors upon injection into athymic nude mice.