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n-nitrosonornicotine nnn tobacco-specific nitrosamine tobacco group carcinogen human cancer smokeless chewing snuff cigarettes cigars betel quid nitrosation nornicotine properties stimulant exposure cytochrome p450 synthesis smoking heart liver lungs 3d poison venom toxicant toxic toxicity toxin toxicology poisoning danger hazard harmful kill limit antidote intoxication detoxification carcinogenicity carcinogenic tumor promotion malignancy angiogenesis