We previously reported the chemopreventive potential of kava against 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK)andbenzo(a)pyrene (BaP)–induced lung tumorigenesis inA/Jmiceduring the initiation and postinitiation stages. In this study, we investigated the tumorigenesis-stage specificity of kava, thepotential active compounds, and theunderlyingmechanisms inNNK-induced lung tumorigenesis ...

4-(A/-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major nitrosamine formed in tobacco smoke, induces a high incidence of lung, liver, and nasal cavity tumors in rats. Since «hydroxylation of NNK by target tissues can lead to the generation of a methylating agent, the formation and removal of 7-methylguanine and the promutagenic lesions O6-methylguanine (O6mGua) and 0"-methyldeoxyth...

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1) is a potent tobacco-specific lung carcinogen believed to play a key role in the development of lung cancer in smokers. Metabolic activation of NNK to DNA damaging reactive intermediates proceeds via α-hydroxylation pathways. The end products of these pathways are excreted in the urine of smokers as 4-oxo-4-(3-pyridyl)butanoic acid (keto ac...

Two major metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were previously shown to be highly persistent in human urine after cessation of cigarette smoking. We hypothesized that NNK or its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), was sequestered in the lung. In this study, we further evaluated this hypothesis by q...

Thiamin is indispensable for the normal function of pancreatic acinar cells. These cells take up thiamin via specific carrier-mediated process that involves thiamin transporter-1 and -2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3 genes, respectively). In this study we examined the effect of chronic exposure of pancreatic acinar cells in vitro (pancreatic acinar 266-6 cells) and in vivo ...

BACKGROUND Improved understanding of lung cancer development and progression, including insights from studies of animal models, are needed to combat this fatal disease. Previously, we found that mice with a knockout (KO) of G-protein coupled receptor 5A (Gprc5a) develop lung tumors after a long latent period (12 to 24 months). METHODOLOGY/PRINCIPAL FINDINGS To determine whether a tobacco carc...

Background Fetal alcohol spectrum disorder (FASD) is associated with impairments in insulin and insulin-like growth factor (IGF) signaling through Akt pathways and altered expression of neuro-glial proteins needed for structural and functional integrity of the brain. However, alcohol abuse correlates with smoking, and tobacco smoke contains 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), ...

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is activated to DNA alkylating species via two different alpha-hydroxylation pathways. Methylene hydroxylation leads to DNA methylation, whereas methyl hydroxylation yields DNA pyridyloxobutylation. We have developed a high-pressure liquid chromatography assay utilizing radiochemical detection that permits the determination of the extent of m...

PURPOSE There is a need to identify lung cancer prevention mechanisms. All-trans-retinoic acid (RA) was reported previously to inhibit N-nitrosamine-4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK) carcinogenic transformation of BEAS-2B human bronchial epithelial cells (J. Langenfeld et al., Oncogene, 13: 1983-1990, 1996). This study was undertaken to identify pathways targeted during this ...

BACKGROUND In 1996, an estimated 15,700 new cases of cancer of the uterine cervix and 4,900 deaths from this disease were expected to occur in the United States. In a recent international study, human papillomavirus DNA was found in more than 90% of cervical tumor specimens examined, irrespective of the nationality of the patients from whom the samples were obtained. Although infection with hum...