Metabolism of Deuterated NNN in Smokeless Tobacco Users

The purpose of this study is to better understand how people break down a tobacco specific cancer-causing toxin called N'-nitrosonornicotine (NNN) that is present in smokeless tobacco and cigarettes. Some people are able to get rid of this chemical as a harmless agent better than others. Through this research, the investigators hope to develop a better understanding of how people process potentially harmful chemicals and identify tobacco users who are in danger of developing cancer. Participants will complete questionnaires regarding their health and smoking history. The investigators will take blood samples, saliva samples, cheek cells and urine to measure exposure to toxins and harmful chemicals present in smokeless tobacco. Participants will be given smokeless tobacco study product and be asked to use only it for the entire time they are in the study. The study product contains deuterated NNN. Deuterated NNN is just like the NNN found in commercially available smokeless tobacco products, but is labeled with deuterium or heavy hydrogen atoms. Deuterium is non-toxic and safe. Using smokeless tobacco containing deuterium allows us to follow NNN as it is broken down in the body.

Fifty healthy smokeless tobacco users will be recruited by advertising in Minneapolis-St. Paul area. This research will be conducted at the Tobacco Research Center at the University of Minnesota. Regular smokeless tobacco users will be screened over the phone. If eligible after the phone screen, participants will be invited to attend an orientation visit in the clinic where consent will be obtained and subjects will fill out forms about their tobacco use and medical history. Subjects who are determined to be eligible after the orientation visit will return to the clinic for a baseline visit where they will receive the smokeless tobacco product and be instructed to use only the study product until they return for their first lab session seven days later.

Prior to each of the three lab sessions, subjects will collect all of their urine for the 24 hours leading up to their scheduled appointment. At each lab session, participants will use the study product and collect their saliva and tobacco juices at regular intervals. Participants will also swab the inside of their cheek for cells and have their blood drawn.

Collected samples will be used to characterize the metabolic activation and DNA binding of NNN.

Eligibility Criteria:
Inclusion Criteria:

* Regular smokeless tobacco user
* Good physical health with no unstable medical conditions
* Stable and good mental health, i.e., currently do not experience unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria, during the past six months
* Willing to perform study activities such as having blood sample drawn, saliva collection, urine collection, multiple clinic visits
* For female subjects of child bearing potential, not known to be pregnant or nursing, or planning to become pregnant within next 12 months
* Provide written informed consent

Exclusion Criteria:

* Using other tobacco or nicotine containing products
* Unstable medical condition
* Currently taking any medications that affect relevant metabolic enzymes
* Not willing to use switch smokeless tobacco brand to use tobacco enriched with \[pyridine-D4\](S)-NNN for the course of this study