Brand specific responses to smokeless tobacco in a rat lip canal model.

ABSTRACT

BACKGROUND: Different compositions of smokeless tobacco (ST) are widely thought to cause oral carcinoma at different rates but there is little direct evidence for this hypothesis. METHODS: We used a rat lip canal model to examine the mucosal changes induced by chronic daily exposure to four different brands of ST Skoal, Copenhagen, Ettan Swedish Snus, and Stonewall, differing in measured levels of tobacco specific nitrosamines (TSNAs), unprotonated nicotine, moisture, and pH. RESULTS: Exposure to the lip canal for 12 months produced changes in the mucosa marked by increases in S phase and M phase cells for the Skoal and Copenhagen exposed rats. This correlated with the high level of TSNAs and nicotine in these products. All the tobacco products, to different degrees, induced sites of moderate to severe dysplasia some with extensive rete peg outgrowth from the oral mucosa not seen in the controls. Many of these sites showed a loss of p16 expression. CONCLUSIONS: While all ST products caused dysplasia, the products with lower levels of TSNAs and unprotonated nicotine caused less, consistent with the model that tobacco with low levels of nitrosamines might potentially induce fewer carcinomas in human users.