Mutagenic activity in smokeless tobacco products sold in the USA.

Aqueous extracts of smokeless tobacco products (snuff, chewing tobacco, smokeless tobacco) sold in the USA are mutagenic in the base-pair substitution mutant, Salmonella typhimurium TA100, with potencies of 8000-16,000 revertants/g tobacco. Most of the activity failed to extract into organic solvents at neutral pH and a portion of the activity extracted into organic solvents at acidic pH. The tobacco-specific nitrosamines, N-nitrosonornicotine and (4-methylnitrosamino)-1-(3-pyridyl)-1-butanone did not exhibit this behavior. Mutagenesis required metabolic activation (liver S-9 fraction plus NADPH) and a weakly acidic liquid preincubation. The mutagenesis behavior is typical of nitrosamines, and suggests that N-nitrosamines are responsible for at least some of the mutagenic activity in the extracts.