Lechner J F, Tokiwa T, McClendon I A, Haugen A
Carcinogenesis. 1984 Dec;5(12):1697-703. doi: 10.1093/carcin/5.12.1697.
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.
流行病学研究表明，吸入镍化合物会增加人类患呼吸道癌症的风险。将正常人支气管上皮细胞培养物持续暴露于一定剂量（5 - 20微克/毫升）的硫酸镍中，该剂量会使细胞集落形成效率降低30 - 80%。培养40天后，培养物中出现了大的鳞状细胞；未观察到有丝分裂细胞。然后将细胞置于不含硫酸镍的培养基中培养。在总共培养40 - 75天后，有丝分裂细胞集落以每100000个原本处于风险中的细胞产生1个集落的速率出现；在对照培养物或暴露于低于5微克硫酸镍/毫升90天的培养物中未出现集落。从五个实验中分离出的12个经硫酸镍改变的细胞培养物已扩大培养为大规模培养物。大多数细胞系具有增加的群体倍增潜能（大于50次分裂）。一些细胞系在鳞状（终末）分化过程中表现出异常，而另一些细胞系在克隆生长时对表皮生长因子的需求丧失。还观察到非整倍体和标记染色体。然而，这些经硫酸镍改变的细胞培养物均不具有不依赖贴壁生长的特性，将其注射到无胸腺裸鼠体内也不会产生肿瘤。
