Penetration of N-nitrosonornicotine (NNN) across oral mucosa in the presence of ethanol and nicotine

The effects of ethanol concentrations of 5, 15, 20, 25, 27, 30 and 50% on t he penetration of the tobacco-specific carcinogen, nitrosonornicotine (NNN) , across porcine oral mucosa were examined using an in vitro perfusion syst em. Concentrations of ethanol of 25% and above significantly increased the permeability of oral mucosa to NNN, although this increase ceased with 50% ethanol, possibly due to a fixative effect. Nicotine is a consistent compon ent of smoked and smokeless tobacco; the presence of 0.2% nicotine signific antly increased the permeability of oral mucosa to NNN and 2% nicotine caus ed a further increase. Combined use of nicotine and ethanol significantly i ncreased the penetration of NNN across oral mucosa over that of ethanol alo ne until the concentration of ethanol reached 50%. The results of this stud y suggest that the synergy between tobacco and alcohol in the etiology of o ral cancer may be explained, at least in part, by the local permeabilizing effects of alcohol on the penetration of tobacco-specific (and other) carci nogens across oral mucosa.