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Evidence for cytochrome P450 2A6 and 3A4 as major catalysts for N'-nitrosonornicotine alpha-hydroxylation by human liver microsomes.

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The tobacco specific carcinogen N'-nitrosonornicotine (NNN), is believed to be a causative agent for esophageal cancer in smokers. NNN requires metabolic activation to exert its carcinogenic potential. Metabolism occurs through cytochrome P450 (P450) catalyzed 2'- and 5'-hydroxylation, which

Chemical studies on tobacco smoke LVI. Tobacco specific nitrosamines: origins, carcinogenicity and metabolism.

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Tobacco contains specific carcinogenic nitrosamines which are derived from nicotine. These compounds may be among the causative agents for the various cancers (lung, oral cavity, oesophagus, bladder and pancreas) which are associated with tobacco usage. The major tobacco specific nitrosamine is

Metabolism in the F344 rat of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, a tobacco-specific carcinogen.

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The metabolism of the tobacco-specific carcinogen, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was studied in the F344 rat, in which it induces tumors of the nasal cavity, liver, and lung. When NNK was incubated with rat liver microsomes and a reduced nicotinamide adenine dinucleotide

Lack of correlation between DNA methylation and hepatocarcinogenesis in rats and hamsters treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

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Previous studies have demonstrated that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced liver tumors in F344 rats but not in Syrian golden hamsters. The aim of this study was to determine whether there was a correlation between the persistence of

Two types of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone hemoglobin adducts, from metabolites which migrate into or are formed in red blood cells.

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The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), is considered to play an important role in the induction of lung cancer in tobacco users. In rats treated with [5-3H]NNK, 20 to 40% of the tritium bound to hemoglobin (Hb) is released by base hydrolysis as

Role of CYP2A13 in the bioactivation and lung tumorigenicity of the tobacco-specific lung procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: in vivo studies using a CYP2A13-humanized mouse model.

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The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is abundant in tobacco smoke, is a potent lung procarcinogen. The present study was aimed to prove that transgenic expression of human cytochrome P450 2A13 (CYP2A13), known to be selectively expressed in the

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