Schüller H M, Nylen E, Park P, Becker K L
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
Life Sci. 1990;47(6):571-8. doi: 10.1016/0024-3205(90)90618-2.
Neuroendocrine hamster lung tumors, induced by exposure to 60% hyperoxia and subcutaneous administration of the tobacco-specific nitrosamine 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) for 12 weeks, were placed in cell culture. By subsequent selective transfer of epithelial cells and maintenance in an atmosphere of 8% CO2, cell lines with characteristics of neuroendocrine cells were established. The neuroendocrine markers expressed by these cell lines included electron dense neuroendocrine secretion granules as well as secretion of calcitonin and mammalian bombesin. In keeping with data previously reported for a human neuroendocrine lung tumor cell line, nicotine, acetylcholine, and mammalian bombesin (MB) acted as strong growth factors in these neuroendocrine hamster tumor lines. The mitogenic effect of nicotine and acetylcholine was abolished by nicotinic receptor inhibition while the effects of mammalian bombesin were inhibited by an antagonist of MB receptors. Our data suggest that a receptor-mediated mitogenic effect of nicotine on neuroendocrine lung cells may be instrumental in the induction of smoking-associated small cell lung cancer.
将暴露于60%高氧环境并皮下注射烟草特异性亚硝胺4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁酮（NNK）12周诱导产生的神经内分泌仓鼠肺肿瘤置于细胞培养中。通过随后上皮细胞的选择性转移并在8%二氧化碳的气氛中培养，建立了具有神经内分泌细胞特征的细胞系。这些细胞系表达的神经内分泌标志物包括电子致密神经内分泌分泌颗粒以及降钙素和哺乳动物蛙皮素的分泌。与先前报道的人类神经内分泌肺肿瘤细胞系的数据一致，尼古丁、乙酰胆碱和哺乳动物蛙皮素（MB）在这些神经内分泌仓鼠肿瘤细胞系中作为强大的生长因子起作用。尼古丁和乙酰胆碱的促有丝分裂作用通过烟碱受体抑制而消除，而哺乳动物蛙皮素的作用则被MB受体拮抗剂抑制。我们的数据表明，尼古丁对神经内分泌肺细胞的受体介导的促有丝分裂作用可能在吸烟相关的小细胞肺癌的诱导中起作用。
