title: Potential nitrite scavengers as inhibitors of the formation of N-nitrosamines in solution and tobacco matrix systems.
abstract: The ability of 20 compounds, all but one tobacco constituents, to inhibit the formation of tobacco-specific N-nitrosamines (TSNA) was investigated in buffer and detergent solution and in tobacco midrib and lamina systems. In solution at pH 5.5, ascorbic acid and the phenolic acids caffeic and ferulic acid were the most potent inhibitors of the reaction between nornicotine and nitrite, with nearly complete inhibition at molar ratios test compound/nitrite > 1:1. Also, cysteine > dihydrocaffeic acid > protocatechuic acid approximately catechin acted as strong inhibitors with >90% inhibition at a ratio of 3:1. Lower inhibitions were observed with chlorogenic acid > p-coumaric acid > sclareol > serine. Rutin showed an inhibition of 34% at a ratio of 0.1:1. Sclareol, alanine, proline, and serine did not significantly affect the N-nitrosonornicotine (NNN) formation. alpha-Tocopherol and glutathione enhanced NNN formation at pH 5.5 but were inhibitors at pH 3. Cinnamic acid, vanillic acid, eugenol, and esculin enhanced NNN formation. Increased NNN formation was also observed for dihydrocaffeic acid, chlorogenic acid, protocatechuic acid, and catechin at a less-than-equimolar ratio of test compound to nitrite. The tobacco matrix experiments were performed with air-cured, ground tobacco midrib and lamina. Caffeic acid, ferulic acid, dihydrocaffeic acid and catechin were potent inhibitors of the formation of TSNA in the midrib as well as in the lamina. Also protocatechuic acid, glutathione, ascorbic acid, p-coumaric acid, chlorogenic acid and cysteine were inhibitors, while alpha-tocopherol and rutin inhibited the reaction in the midrib but not in the lamina. Cinnamic acid, vanillic acid, eugenol, alanine, proline and serine showed small effects only. The molar ratio of secondary alkaloid(s)/nitrite in the test systems were 0.1:1 (solution), approximately 0.25:1 (midrib), and approximately 1:1 (lamina) and is most likely the major contributor to the observed order of inhibition potency (solution > midrib > lamina) of the test compounds. The vicinal phenolic hydroxyl groups of polyphenols and the simultaneous presence of a phenol group and an olefinic bond in hydroxycinnamic acids were the most characteristic structural elements of the potent inhibitors.
authors.affiliation: Research & Analysis, Swedish Match, SE-118 85 Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Rundlöf
authors.forename: E
authors.initials: E
authors.lastname: Olsson
authors.forename: A
authors.initials: A
authors.lastname: Wiernik
authors.forename: S
authors.initials: S
authors.lastname: Back
authors.forename: M
authors.initials: M
authors.lastname: Aune
authors.forename: L
authors.initials: L
authors.lastname: Johansson
authors.forename: I
authors.initials: I
authors.lastname: Wahlberg
mesh_terms: D016166:Free Radical Scavengers / Q000494:pharmacology*; D009573:Nitrites / Q000737:chemistry*; D009603:Nitroso Compounds / Q000138:chemical synthesis*; D010947:Plants, Toxic; D012996:Solutions; D014026:Nicotiana / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D009573:Nitrites; D009603:Nitroso Compounds; D012996:Solutions