Impact of Genetics and Production Practices on Tobacco-Specific Nitrosamine Formation

Tobacco (Nicotiana tabacum L.) plants biochemically synthesize multiple alkaloid compounds. The predominant compound, nicotine, and other alkaloids in the plant can be nitrosated to form tobacco-specific N-nitrosamines (TSNAs). TSNAs are found in cured tobacco leaf and are created primarily during the curing process. Some TSNAs have been classified by regulatory authorities as human carcinogens. Therefore, the mechanisms associated with TSNA formation in tobacco have long attracted research and industry interest. This chapter describes TSNA formation and factors affecting TSNA levels in tobacco, including alkaloid biosynthesis, nitrite compounds, tobacco type, TSNA formation propensity, environmental conditions, and production practices. It further expounds on the genetic aspects related to TSNA formation and TSNA-mitigation methods, such as the use of low-alkaloid tobacco lines, alteration of gene expression in alkaloid biosynthesis genes and regulatory genes, and nicotine transport mechanisms. Discovery of nicotine demethylase and reductions in N-nitrosonornicotine through down-regulation or knockout of genes encoding nicotine demethylase are described. Research and industry efforts to mitigate TSNA formation in the cured leaf and tobacco products are also discussed.