NNK EFFECTS ON RECEPTOR PATHWAYS IN LUNG CELLS

描述：神经内分泌癌和周围腺癌是 最常见的组织学肺癌类型与吸烟有关。这个 尼古丁亚硝胺，4-(甲基亚硝基)-1-(2-吡啶)-1- 丁酮(NNK)是最丰富和最有效的致癌物之一 包含在香烟烟雾中。NNK导致高发病率 实验室啮齿动物肺部周围性腺癌持续存在 在环境空气条件下，虽然它会导致肺癌 高氧仓鼠的神经内分泌分化。 已经证明NNK与烟碱胆碱能和β-肾上腺素能结合 仓鼠肺癌和肺癌细胞系中的受体 建议研究NNK在有丝分裂信号转导中的作用 受这些受体类型刺激的通路。特定目标 已经证明NNK诱导的细胞系有丝分裂起源于 周围型肺腺癌与β-肾上腺素能结合 舒勒博士将研究受体(b-AR)和环磷酸腺苷的激活 NNK对该信号转导通路的急性和慢性影响 用正常和NNK转化的人支气管细胞和 正常仓鼠Clara细胞以及来源于人和 以仓鼠肺腺癌为模型系统。

DESCRIPTION: Neuroendocrine cancer and peripheral adenocarcinoma are the most common histological lung cancer types linked with smoking. The nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(2-pyridyl)-1- butanone (NNK) is among the most abundant and potent carcinogens contained in cigarette smoke. NNK induces a high incidence of peripheral adenocarcinomas in the lungs of laboratory rodents maintained under ambient air conditions while it causes lung cancers of neuroendocrine differentiation when administered to hyperoxic hamsters. Having shown that NNK binds to nicotinic cholinergic and beta-adrenergic receptors in hamster lung and lung cancer cell lines Dr. Schuller proposes to study the effects of NNK on mitogenic signal transduction pathways stimulated by these receptor types. Specific Aim Having shown that NNK-induced mitogenesis of cell lines derived from peripheral pulmonary adenocarcinomas involves binding to beta adrenergic receptors (b-AR) and activation of cyclic AMP, Dr. Schuller will study the acute and chronic effects of NNK on this signal transduction pathway in vitro using normal and NNK transformed human bronchial cells and normal hamster Clara cells as well as cell lines derived from human and hamster lung adenocarcinomas as model systems.