Tobacco-specific nitrosamines: formation from nicotine in vitro and during tobacco curing and carcinogenicity in strain A mice.
The formation of tobacco-specific nitrosamines from the major tobacco alkaloid nicotine was examined. Detached leaf tobacco was fed either [2'-14C]nicotine or [2'-14C]nornicotine and air cured. The cured leaf was then analyzed for [2'-14C]N'-nitrosonornicotine ([2'-14C]NNN). The yield of [2'-14C]NNN was 0.007% from nornicotine and 0.009% from nicotine. Because the ratio of nicotine to nornicotine in conventional nicotine-type tobacco is 20-100:1, nicotine is considered to be the major precursor for the carcinogen NNN in tobacco. The formation of other nitrosamines from nicotine in vitro was then studied. Reaction of nicotine with NaNO2 gave rise to NNN, as well as to two other nitrosamines, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butanal (NNA). Analysis of market products revealed the presence of NNK (0.6-24 microgram/g) in chewing tobacco and snuff. The tumorigenic activity of NNN, NNK, and NNA in strain A mice was studied. NNK induced more lung adenomas per mouse than did NNN, whereas NNA was less active than NNN. In addition, two cases of undifferentiated carcinoma of the salivary glands occurred in the NNN experimental groups.
D000236:Adenoma / Q000139:chemically induced*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000139:chemically induced*; D051379:Mice; D008805:Mice, Inbred A; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009538:Nicotine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D009602:Nitrosamines / Q000378:metabolism*; D010947:Plants, Toxic; D011725:Pyridines / Q000378:metabolism; D014026:Nicotiana / Q000378:metabolism*
C016582:4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butanal; D009602:Nitrosamines; D011725:Pyridines; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine