Figure 1.

Tobacco-specific N-nitrosamines are formed by the N-nitrosation of nicotine. NNN (N′-nitrosonornicotine) and NNK (4-(metylnitrosamino)-1-(3-pyridyl)-1-butanon) are the most potential carcinogens formed by nicotine from cigarette smoke. NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) is a metabolite from the reduction of NNK and total NNAL (NNAL and its glucuronides) in urine and can be used to examine the possible role of N-nitrosamines metabolites in tumor development. Nicotine metabolites carcinogens may induce multiple mutations in critical genes, such as p53, KRAS, p16, and Rb. A permanent mutation occurs in these critical genes that can contribute to activation of the oncogene or blockade of the tumor suppressor gene. Multiple aberrant events can continue to cause cells with abnormal regulation and eventually lung cancer progression.