Biomaterial Database

Metabolism of the tobacco specific nitrosamines, N'-nitrosonornicotine and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone. 1980

S S Hecht, and C B Chen, and R Young, and D Lin, and D Hoffmann

The metabolism, in the F-344 rat, of the tobacco-specific carcinogens, N'-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was studied. NNN was hydroxylated at each position of the pyrrolidine ring; 2'-hydroxylation gave 4-hydroxy-1-(3-pyridyl)-1-butanone in vitro and the corresponding acid in vivo, 3'-hydroxylation gave 3'-hydroxyNNN, 4'-hydroxylation gave 4'-hydroxy-NNN and 5'-hydroxylation gave 4-hydroxy-4-(3-pyridyl)butanal (in vitro) and 4-hydroxy-4-(3-pyridyl) butanoic acid (in vivo). The principle ring hydroxylation in the untreated F-344 rat was 5'-hydroxylation. Pyridine N-oxidation was also observed, giving NNN-1-N-oxide as a major metabolite. The principle urinary metabolites of NNN were formed by 5'-hydroxylation and pyridine-N-oxidation. For NNK, a major process was reduction of the carbonyl to give 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanol. alpha-Hydroxylation of both the N-methyl and N-methylene groups was also observed, as was formation of NNK-N-oxide in vitro and in vivo.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D009538	Nicotine	Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.	Nicotine Bitartrate,Nicotine Tartrate
D009602	Nitrosamines	A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties.	Nitrosamine
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D010947	Plants, Toxic	Plants or plant parts which are harmful to man or other animals.	Plants, Poisonous,Plant, Poisonous,Plant, Toxic,Poisonous Plant,Poisonous Plants,Toxic Plant,Toxic Plants
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D006900	Hydroxylation	Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)	Hydroxylations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.