Smokeless Tobacco and Oral Cancer: An Assessment of Evidence Derived from Laboratory Animals

Abstract

No carcinogenic activity was observed when snuff was inserted into the cheek pouch of the hamster or spread over the oral mucosa. This negative result was obtained in a number of experiments whether snuff was applied once only and left in place for several months or inserted repeatedly for up to 2 years. In the rat, a few tumours were observed when snuff was inserted into the artificial lip canal. The insertion appeared to cause a considerable reaction in the surrounding tissue so it is plausible to assume that trauma plays an important role in the development of these tumours. An extract of snuff applied to the oral mucosa of the rat did not produce any tumours, but an extract enriched by the addition of 10 times the naturally-occurring amounts of NNN and NNK produced a few benign tumours at the site of application. A higher incidence of tumours was produced when an equivalent amount of an aqueous solution of these two nitrosamines was applied directly to the oral mucosa, suggesting, according to the authors, that snuff inhibits the carcinogenic activity of TSNAs. Initiation/promotion studies were carried out on snuff in the rat in order to explore further its carcinogenic potential. The results were consistent with the conclusion that snuff does not possess any promotional activity. No increase in tumour incidence was observed in mice when snuff was given in the diet at concentrations of 25% gradually decreasing to 5% in a 14 month study. A negative result was also obtained in the rat given snuff at a concentration of 5% for 18 months. In hamsters given snuff at a concentration of 20% for 2 years, forestomach tumours occurred. A comparable incidence of this type of tumour occurred in animals given 20% cellulose. The result of this study does not provide valid evidence of carcinogenicity. HSV and snuff applied orally in the hamster produced a high incidence of squamous cell carcinomas. The sustained high level of squamous cell hyperplasia generated by the experimental design could account for the development of these tumours. Despite the defects in some of the earlier studies, the sum total of this experimental work suggests that snuff is not carcinogenic to the oral mucosa of the hamster or the rat. It is also unlikely to cause tumours in other tissues in these species. These results give some degree of reassurance that snuff is not likely to be carcinogenic to the human oral mucosa. The interaction of snuff and HSV viruses is, at the moment, questionable and requires further investigation.