Chemoprevention of aerodigestive tract cancers: Investigation of food-based and single-agent approaches to the prevention of chemically-induced tumorigenesis in rodents.

摘要

Estimates of cancer incidence in the United States for 2001 indicate that 18% of all cancers diagnosed will originate in the aerodigestive tract, including the larynx, lung and bronchus, oral cavity, pharynx and esophagus. In addition, aerodigestive tract cancers are predicted to cause over 180,000 deaths this year. Our laboratory has evaluated the chemopreventive potential of certain whole foods and a variety of single agents, including food-derived and synthetic compounds, in animal models of lung and esophageal cancers. These studies were conducted to determine the efficacy and toxicity of whole food preparations and single agents, with the ultimate goal of establishing candidate chemopreventives for use in high risk populations accrued for human clinical trials. In addition to chemoprevention, our studies provide experimental support for other means of cancer prevention, including the development or modification of dietary recommendations for the general population. Whole foods, particularly fruits and vegetables, provide complex mixtures of preventive compounds which may be active at multiple stages of carcinogenesis or have additive or synergistic effects. According to a food-based strategy for cancer chemoprevention, we conducted a study to evaluate a freeze-dried preparation of strawberries in nitrosamine- and polycyclic aromatic hydrocarbon-induced mouse lung tumorigenesis. A single-agent strategy for cancer chemoprevention typically involves the use of an agent which targets a specific process in carcinogenesis. We conducted a study which indicated that cyclooxygenase (COX) overexpression may play an important role in the development of tumors in a rat model of human esophageal cancer. Based on our findings, we evaluated the effect of piroxicam, a potent COX inhibitor, on post-initiation events of nitrosamine-induced rat esophageal tumorigenesis. The results of our studies indicated that freeze-dried strawberries and piroxicam were ineffective inhibitors of tumorigenesis in the mouse lung and rat esophagus, respectively. Together, our findings illustrate the potential of certain chemopreventives to produce remarkably diverse effects among animal model systems—and suggest the importance of developing mechanism-based chemopreventives which inhibit multiple processes in carcinogenesis.