Stereospecific Deuterium Substitution Attenuates the Tumorigenicity and Metabolism of the Tobacco-Specific Nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

• Published in: Chemical research in toxicology Vol. 16; no. 6; pp. 794 - 806
• Main Authors: Jalas, John R, McIntee, Edward J, Kenney, Patrick M. J, Upadhyaya, Pramod, Peterson, Lisa A, Hecht, Stephen S
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.06.2003
• Subjects: Animals; Aryl Hydrocarbon Hydroxylases - metabolism; Carcinogens - metabolism; Carcinogens - toxicity; Cytochrome P-450 CYP2A6; Deuterium - chemistry; DNA - metabolism; DNA Adducts - analysis; Dose-Response Relationship, Drug; Female; Guanine - analogs & derivatives; Guanine - metabolism; Lung - drug effects; Lung - enzymology; Lung Neoplasms - chemically induced; Lung Neoplasms - pathology; Mice; Mice, Inbred A; Microsomes - enzymology; Mixed Function Oxygenases - metabolism; Molecular Structure; Nitrosamines - chemistry; Nitrosamines - metabolism; Nitrosamines - toxicity; Stereoisomerism; Structure-Activity Relationship

Stereochemical determinants of the tumorigenicity and metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were investigated using the stereospecifically deuterated isotopomers (4R)-[4-2H1]NNK and (4S)-[4-2H1]NNK. Upon ip administration to groups of 20...