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

Epidemiological studies have shown that inhalation of nickelcompounds enhances the risk of human respiratory cancer. Culturesof normal human bronchial epithelial cells were continuouslyexposed to a dose (5–20 µg/ml) of NiSO₄ that reducedtheir colony forming efficiency by 30–80%. After 40 daysof incubation, the cultures consisted of large, squamous cells;mitotic cells were not observed. The cells were then maintainedin medium without NiSO₄. After 40–75 total days of incubation,colonies of mitotic cells appeared at a rate of 1 colony per100 000 cells originally at risk; no colonies appeared in controlcultures or in cultures exposed to <5 µg NiSO₄/ml for90 days. Twelve NiSO₄-altered cell cultures isolated from fiveexperiments have been expanded into mass cultures. Most of thecell lines have an increased population doubling potential (>50divisions). Some exhibit aberrations in the squamous (terminal)differentiation process whereas others have lost the requirementfor epidermal growth factor for clonal growth. Aneuploidy andmarker chromosomes have also been noted. However, none of theseNiSO₄-altered cell cultures are anchorage independent nor dothey produce tumors upon injection into athymic nude mice.