title: 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.
authors.affiliation: Department of Oral Medicine and Diagnostics, University of Illinois at Chicago, Chicago, IL 60612-7213,USA. joschwar@uic.edu
authors.forename: Joel L
authors.initials: JL
authors.lastname: Schwartz
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Brunnemann
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Adami
authors.forename: Suchismita
authors.initials: S
authors.lastname: Panda
authors.forename: Sara C
authors.initials: SC
authors.lastname: Gordon
authors.forename: Dietrich
authors.initials: D
authors.lastname: Hoffmann
authors.forename: Guy R
authors.initials: GR
authors.lastname: Adami
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006863:Hydrogen-Ion Concentration; D007124:Immunoenzyme Techniques; D008046:Lip / Q000187:drug effects*; D009061:Mouth Mucosa / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000032:analysis; D009538:Nicotine / Q000032:analysis; D009602:Nitrosamines / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014030:Tobacco, Smokeless / Q000009:adverse effects* / Q000737:chemistry*
chemical_list: D009363:Neoplasm Proteins; D009602:Nitrosamines; D018809:Proliferating Cell Nuclear Antigen; D009538:Nicotine