Cell type specific, receptor-mediated modulation of growth kinetics in human lung cancer cell lines by nicotine and tobacco-related nitrosamines.

The objective of this study was to investigate a potential involvement of nicotinic cholinergic receptors in the mediation of cell type specific biological effects of nicotine and the two tobacco-related nitrosamines N-nitrosodiethylamine (DEN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on human lung cells. Three well differentiated human lung cancer cell lines that have been reported previously to possess ultrastructural and biochemical features of normal pulmonary neuroendocrine cells, Clara cells and alveolar type II cells, respectively, were used for these experiments. The effects of nicotine, DEN, and NNK on cell proliferation and its modulation by established antagonists of nicotinic and muscarinic cholinergic receptors were studied. In the neuroendocrine cell line, nicotine and the two nitrosamines caused a strong stimulation of cell proliferation that was inhibited by antagonists of nicotinic cholinergic receptors. In the cell lines with features of Clara cells and alveolar type II cells, nicotine did not stimulate cell proliferation. Both nitrosamines stimulated cell proliferation in the cell line with Clara cell features. This effect was not changed by pre-exposure to cholinergic antagonists. The data suggest a selective uptake of nicotine and the two nitrosamines via nicotinic cholinergic receptors in pulmonary neuroendocrine cells.