Using Untargeted Metabolomics to Reveal Commonalities in Metabolic Reprogramming Events Between Tobacco Use and Oral Cancer

Tobacco usage remains one of the leading causes of death both in the United States and worldwide. One of the biggest negative health outcomes associated with tobacco usage is cancer including Oral Cancer. One of the main hallmarks of cancer is metabolic reprogramming with several metabolic changes seen through all stages of the cell cycle. These changes result in the cancer cell having advantages in both growth and survivability in comparison to healthy cells. Tobacco and it’s smoke has many different chemicals that can impact cellular metabolism, with the most notable being carcinogens. When cells are exposed to these chemicals it can cause severe metabolic changes including cancer. The main goal of this project was to compare healthy oral cell metabolism with oral cancer cell metabolism and to see if these changes can be seen in those exposed to tobacco. This project is an accumulation of different studies performed on either the relationship between smoking and metabolism or oral cancer and metabolism.The NIST study is based on two urine reference materials purchased from the national institute of standards and technology. The two products were a pool of urine from smokers and a pool of urine from non-smokers. Tissue Microarrays are one of the most common tissue sample types distributed by hospitals and can hold a wide variety of tissue types from many patients. CAL-27 is an oral cancer cell line that can be easily grown. NNK is one of the carcinogens found in tobacco smoke. Exposing cells to NNK can be used to simulate exposure to tobacco smoke but since NNK is only one of many carcinogens in tobacco smoke, its not a perfect one to one comparison but it allows for the understanding of how oral cells react to being exposed to tobacco carcinogens. Three super pathways (amino acid metabolism, carbohydrate metabolism and oxidative phosphorylation, and vitamin metabolism all have alterations in all of the different studies performed. The metabolic pathways that were found to be altered in both tobacco users and those with oral cancer can viewed as possible mechanisms for how smoking leads to oral cancer development. They may also be used as potential biomarkers in smokers that show that they are at a higher risk of oral cancer in comparison to other tobacco users. More research needs to be done in the future to validate the role of these metabolic perturbations in response to smoking and/or oral cancer development.Bachelor of Science in Public Healt