Abstract：
Tobacco-specific nitrosamines (TSNA) have implications in the pathogenesis of various lung diseases and conditions are prevalent even in non-smokers. N-nitrosonornicotine (NNN) and 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent pulmonary carcinogens present in tobacco product and are mainly responsible for lung cancer. TSNA reacts with pulmonary surfactants, and alters the surfactant phospholipid. The present study was undertaken to investigate the in vitro exposure of rat lung tissue slices to NNK or NNN and to monitor the phospholipid alteration by [(32)P]orthophosphate labeling. Phospholipid content decreased significantly in the presence of either NNK or NNN with concentration and time dependent manner. Phosphatidylcholine (PC) is the main phospholipid of lung and significant reduction was observed in PC ∼61%, followed by phosphatidylglycerol (PG) with 100μM of NNK, whereas NNN treated tissues showed a reduction in phosphatidylserine (PS) ∼60% and PC at 250μM concentration. The phospholipase A2 assays and expression studies reveal that both compounds enhanced phospholipid hydrolysis, thereby reducing the phospholipid content. Collectively, our data demonstrated that both NNK and NNN significantly influenced the surfactant phospholipid level by enhanced phospholipase A2 activity.
摘要：
烟草特异性亚硝胺（TSNA）在各种肺部疾病的发病机理中具有重要意义，即使在非吸烟者中也很普遍。N-亚硝基或烟碱（NNN）和4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）是烟草产品中存在的有效肺部致癌物，主要负责肺癌。TSNA与肺表面活性剂反应,并改变表面活性剂磷脂。本研究旨在研究大鼠肺组织切片在NNK或NNN中的体外暴露，并通过[（32）P]正磷酸盐标记监测磷脂的变化。在存在NNK或NNN的情况下，磷脂含量显着降低，并具有浓度和时间依赖性。磷脂酰胆碱（PC）是肺的主要磷脂，在PC中观察到显着降低〜61％，然后是磷脂酰甘油（PG）和100μM的NNK，而NNN处理的组织在250μM浓度下显示磷脂酰丝氨酸（PS）降低60%，PC降低。磷脂酶A2测定和表达研究表明，这两种化合物都增强了磷脂水解，从而降低磷脂含量。总的来说，我们的数据表明,NNK和NNN均通过增强磷脂酶A2活性显著影响表面活性剂磷脂水平.
