Effects of endogenous and tobacco-related amines and nitrosamines on cell growth and morphology of a cell line derived from a human neuroendocrine lung cancer.

This report is part of a comprehensive research programme to elucidate the role of physiological functions and pathways of pulmonary neuroendocrine cells in the cascade of events that lead to the development of neuroendocrine lung cancer. In this study, a well differentiated neuroendocrine cell line (NCI-H727) derived from a human lung carcinoid was used to investigate the ability of endogenous and tobacco-related amines to stimulate cell proliferation in neuroendocrine tumour cells. Cell line NCI-H727 was exposed in vitro to the endogenous amine serotonin and its precursor 5-hydroxytryptophan (5-HTP), to the tobacco-related amine nicotine, and the tobacco-related nitrosamines N-nitrosodiethylamine (DEN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The experiments were conducted in both 8% CO(2)-92% air and in 5% CO(2)-95% air. The effect on growth kinetics and ultrastructure of these conditions were studied. All amines had a dose-dependent stimulating effect on cell growth when tested in 8% CO(2)-92% air with nicotine exerting the strongest effect. No such effect was observed in 5% CO(2)-95% air and the control cells did not grow under these conditions. DEN, 5-HTP, serotonin and NNK all caused dedifferentiation of cytoplasmic organelles. Nicotine caused a change in size and ultrastructure of dense-cored granules suggestive of a change in the nature of stored neuroendocrine material.