Potent carcinogen isolated from smokeless tobacco
MedWire News: Researchers have identified the chemical in smokeless tobacco that causes mouth and esophageal cancer, and say that there is an "urgent need to eliminate this powerful carcinogen from tobacco products."
Smokeless tobacco products, such as snuff, are made from tobacco leaves and may be inhaled through the nose or chewed in the mouth.
The products are increasingly popular, in part because they are less harmful than cigarette smoking, explain Silvia Balbo (University of Minnesota, Minneapolis, USA) and colleagues. They also avoid the dangers of passive smoking, meaning that they can be consumed in public places.
Nevertheless, they are known to cause cancer of the mouth and esophagus, which led Balbo and team to perform a study in rats aimed at isolating the cancer-causing compounds.
Their work centered on the chemical nitrosonornicotine (NNN), which has a chiral center at its 2'-position and consequently exists as enantiomers. The major enantiomer in tobacco products is (S)-NNN while the other form is (R)-NNN.
The researchers studied four groups of 24 rats: one group had (S)-NNN added to the drinking water, one group had (R)-NNN added, one group had both enantiomers added, and one group drank plain tap water. The rats drank their allocated water daily for 1 year and were observed for a total of 20 months.
Rats that drank (S)-NNN were exposed to roughly the same dose of the chemical as a human would be if they were a longstanding user of smokeless tobacco products, explain Balbo and colleagues.
All 48 rats given water containing (S)-NNN developed cancers in the esophagus and mouth. The rats started to lose weight after about 1 year and all died from their tumors within 17 months of starting the experiment.
Postmortem examination revealed multiple tumors in the animals, with a total of 153 esophageal and 96 mouth tumors being found. Histopathologic analysis of the tumors indicated that they encompassed a spectrum from benign squamous papillomas to malignant squamous cell carcinomas.
Among the 24 rats given water containing (R)-NNN only, five developed mouth cancer and three developed esophageal cancer. All of these animals were still alive 20 months after starting the experiment.
By contrast, none of the rats given plain tap water developed mouth or esophageal cancers or died during the study.
Balbo and colleagues conclude: "These results clearly demonstrate, for the first time, the strong carcinogenicity of (S)-NNN in the rat oral cavity. Thus, (S)-NNN is the only potent oral carcinogen identified in smokeless tobacco.
"If it is not possible to stop the use of smokeless tobacco products, we should advocate for a reduction of this chemical in these products. In addition, we have to understand how this research translates to human beings."
The research was presented at the annual meeting of the American Association for Cancer Research, held in Chicago, Illinois.
By Joanna Lyford