1. Contrary to established metabolic pattern, a recent investigation of NNK metabolism produced in rat urine higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) than their N-oxides, suggesting that reconversion of N-oxides could occur after urine formation. 2. To verify the possible role of bacteria in the reduction of N...

The tobacco-specific carcinogenic nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is formed during the curing and processing of tobacco by nitrosation of nicotine. Nicotine and NNK have structural similarities, and they are both metabolized extensively by lung tissue via several steps known to require oxidative enzyme systems, such as cytochrome P450. On the other hand, nicot...

Tobacco use is a major public health problem worldwide. Tobacco-related cancers cause millions of deaths annually. Although several tobacco agents play a role in the development of tumors, the potent effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are unique. Metabolically activated NNK and NNN induce deleterious mutations in oncogenes and tumor s...

The Family Smoking Prevention and Tobacco Control Act gives the U.S. Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerfu...

The nicotine-derived N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) is abundant in smokeless tobacco and tobacco smoke and is hepatocarcinogenic in F344 rats. We have investigated how vitamin A modulates sister chromatid exchanges and DNA single-strand breaks induced by NNK. In V79 cells, vitamin A at concentrations ranging from 34.9 to 139.6 microM inhibited sister chromat...

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its carbonyl-reduction product, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are potent lung carcinogens in rats and are presumed human lung carcinogens. NNK and NNAL are bioactivated to DNA-binding intermediates via hydroxylation of the carbon atoms adjacent to the nitroso moiety (i.e., -hydroxyl...

Naturally occurring and synthetic isothiocyanates are among the most effective chemopreventive agents known. A wide variety of isothiocyanates prevents cancer in the rat lung, mammary gland, esophagus, liver, small intestine, colon, and bladder. Mechanistic studies have shown that this chemopreventive activity is due to favorable modification of phase I and phase II carcinogen metabolism, resul...

The dose response for O6-methylguanine (O6MG) formation and cytotoxicity was determined in lung and nasal mucosa from Fischer 344 rats during multiple dose administration of the tobacco-specific nitrosamine-4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). O6MG accumulated in the lung following treatment for 12 days with doses of NNK from 0.3 to 100 mg/kg/day. The dose response for NNK...

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a lung-specific tobacco carcinogen. Metabolism is critical to its elimination given its lipophilic nature. Although NNK can be metabolized through detoxification pathways that safely eliminate it from the body, it can also be bioactivated, resulting in the formation of potentially carcinogenic DNA adducts. The isolated perfused rat lung (I...

AIM Epidemiologic studies have demonstrated high rates of smoking among alcoholics, and neuroimaging studies have detected white matter atrophy and degeneration in both smokers and individuals with alcohol-related brain disease (ARBD). These findings suggest that tobacco smoke exposure may be a co-factor in ARBD. The present study examines the differential and additive effects of tobacco-specif...