Epidemiological studies have shown that inhalation of Ni compounds enhances the risk of human respiratory cancer. Cultures of normal human bronchial epithelial cells were continuously exposed to a dose (5-20 .mu.g/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/100,000 cells originally at risk; no colonies appeared in control cultures or in cultures exposed to < 5 .mu.g NiSO4/ml for 90 days. Twelve NiSO4-altered cell cultures isolated from 5 experiments were expanded into mass cultures. Most of the cell lines have an increased population doubling potential (> 50 divisions). Some exhibit aberrations in the squamous (terminal) differentiation process; others have lost the requirement for epidermal growth factor for clonal growth. Aneuploidy and marker chromosomes have also been noted. None of these NiSO4-altered cell cultures are anchorage independent nor do they produce tumors upon injection into athymic nude mice.