Abstract
Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.
Highlights
Numerous studies have shown that cigarette smoking increases the risk of developing pancreatic cancer, its contribution to pancreatitis has only been appreciated in recent years [1,2,3]
Tobacco smoke and its various components, including nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and other tobacco specific nitrosamines have been studied in cells and in vivo [4,5,6,7,8,9,10,11]
It has been reported that roughly 46% of NNN and 26% - 37% of NNK in tobacco are preformed and the remainder is pyrosynthesized from nicotine during smoking [15]
Summary
Numerous studies have shown that cigarette smoking increases the risk of developing pancreatic cancer, its contribution to pancreatitis has only been appreciated in recent years [1,2,3]. Other nitrosamines formed from nicotine include N’-nitrosonornicotine (NNN) and Diethylnitrosamine [13] These nicotine metabolites are potentially formed via nitrosation during processing of the tobacco plant [14]. Other potentially harmful components of tobacco smoke include polycyclic aromatic hydrocarbons, their role in pancreatic disease is undetermined [15,16]. Few reliable animal models of smoking and pancreatic disease have been developed, and little is known about underlying cellular mechanisms. Those that have been established involve exposure of rodents to cigarette smoke in specialized smoke-delivery chambers, or ingestion/injection of a tobacco toxin over a period of time. The subsequent sections will focus on some of these models and underscore the latest developments in our understanding of smoking-related pancreatitis and pancreatic cancer
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