Tobacco Induced Diseases (Oct 2018)
A model of pancreatitis and pancreatic oncogenesis following exposure to Nicotine
Abstract
Cigarette Smoking is a known risk factor for pancreatic cancer. In smokers, increased exposure causes a marked increase in the incidence of these diseases. The mechanism of this effect is yet to be fully understood. We hypothesize that nicotine, a major component of cigarette smoking will have the greatest impact of developing these diseases in smokers. Currently an established animal model is lacking to conduct detailed studies of the etiology of these diseases in smokers. Aim and objective: The aim of our study is to establish a rodent model of pancreatic cancer and to determine the relationships between the development of pancreatitis and pancreatic cancer in response to nicotine exposure. Methods: Adult Male Rats were randomly allocated into treatment groups and acclimatized for at least two weeks with monitored body weight, food and water freely available. Rats were exposed to nicotine in the aerosol chamber designed to deliver aerosol vapor for fixed intervals. At term, rats were fasted, anesthetized and sacrificed. Blood and pancreatic tissues were collected and processed for physiologic studies and for histopathological evaluation. A segment of the pancreas was used for isolation of acinar cells for determination of pancreatic function and for determination of expression and mutation of oncogenes. Alterations of cellular, subcellular and/or genetic mechanisms were studied in isolated pancreatic primary cells applying classical signal transduction pathways. Results showed that nicotine inhaled rats have decreased exocrine pancreatic function and altered pancreatic morphology. These changes are associated and correlated with isolated cell culture data. Conclusions/implications: Data from these studies appear closely related to that reported in patients with pancreatitis. Making rodent as a plausible animal model of pancreatitis and pancreatic cancer will allow us to examine and assess the evolution of this disease process in smokers. Funding UAMS Research Foundation 117-1002531: AWD00050842;
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