Chemical studies on tobacco smoke. XLII. Nitrosonornicotine: presence in tobacco, formation and carcinogenicity.

NNN is the first organic carcinogen isolated from unburned tobacco. It has been found in smoking tobaccos, chewing tobaccos and in snuff in concentrations between 0.3 and 90.0 mug. This appears to be an unusually high concentration for a nitrosamine in an environmental agent. We have presented data which suggest that NNN, and possibly other unknown nitrosamines, are formed during the curing of tobacco and that the nitrate content of tobacco is an important factor in nitrosamine formation. Studies with N'-methylanabasine applied to tobacco plants are currently under way to test the idea that nicotine rather than nornicotine is the major precursor of NNN in processed tobacco. In mice, NNN induces adenomas of the lung. Bioassays with rats have shown that NNN is carcinogenic to the oesophagus and the nasal cavity. These chemical and biological data are consistent with the observation that tobacco chewers face an increased risk of cancer of the oesophagus. This observation does not, of course, rule out the possibility that other tobacco carcinogens are responsible for the increased cancer risk of tobacco chewers.