The tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) both induce nasal tumors in rats and have a common metabolic activation pathway leading to pyridyloxobutylation of DNA. The role of DNA pyridyloxobutylation in rat nasal carcinogenesis has not been evaluated previously. In this study, we used gas chromatography-mass spectrometr...

The nicotine derived jV-nitrosamine 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) is a potent respiratory tract carcinogen in adult Syrian golden hamsters. In this study, the metabolism and genotoxicity of NNK was investigated in fetal hamster trachea and lung tissues. Fetal lung and trachéal explants were cultured in vitro with [5-'H]NNK, and metabolites released into the culture mediu...

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a powerful lung carcinogen in animal models and is considered a causative factor for lung cancer in tobacco users. NNK is stereoselectively and reversibly metabolized to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also a lung carcinogen. Both NNK and NNAL undergo metabolic activation by α...

Recently we reported that the occurrence of lung adenoma caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was completely prevented by pretreatment of female A/J mice with 8-methoxypsoralen, a potent inhibitor of cytochrome P450 (P450 or CYP) 2A [Takeuchi et al. (2003) Cancer Res., 63, 7581-7583]. Thus, the aim of this study was to confirm that 8-methoxypsoralen exhibits chemopreve...

Phenethyl isothiocyanate (PEITC), which occurs in certain cruciferous vegetables, was tested for its ability to inhibit lung tumorigenesis in rats induced by the tobacco-specific nitrosamine 4-(methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in a study involving virtually lifelong administration of both compounds. In addition, two biomarkers of NNK metabolism [4-hydroxy-1-(3-pyridyl)-1-butanon...

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin (Prx) expression induced by NNK during carcinogenesis. Characterization of Prx genes from hamster was performed using bioinformatics. V79 cells were induced with different concentrations of NNK (0.1-0.4 m...

Cigarette smoke is a complex mixture consisting of more than 4500 chemicals, including several tobacco-specific nitrosamines (TSNA). TSNA typically form in tobacco during the post-harvest period, with some fraction being transferred into mainstream smoke when a cigarette is burned during use. The most studied of the TSNA is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK has been show...

The paper by Chen et al. (1) proposes to test the hypothesis that individuals with reduced levels of CYP2D6 (debrisoquine 4-hydroxylase) activity will have a lower risk of anogenital cancer associated with exposure to the tobacco-specific nitrosamine NNK. NNK is a potent carcinogen associated with tobacco-induced cancers in humans. Their rationale is that CYP2D6 can metabolically activate NNK t...

The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), selectively induces lung tumors in F344 rats. NNK is metabolically activated to intermediates that methylate and pyridyloxobutylate DNA. To explore the importance of pyridyloxobutyl DNA adducts in NNK-induced rat lung tumorigenesis, the first study in this report examined levels of these adducts in whole lun...