Cigarette smoking has been investigated as a major risk factor for renal cell carcinoma (RCC). 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most abundant carcinogenic N-nitrosamines present in cigarette smoke. However, the association between repair capacity of NNK-induced DNA damage and RCC risk remains unknown. We used the comet assay to assess whether sensitivity to a N...

Tobacco-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a major environmental risk factor for the pathogenesis of human esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms by which tobacco induces ESCC are not well understood. Na+/Ca2+ exchanger 1 (NCX1) is a plasma membrane transporter protein that plays an essential role in maintaining cytos...

Epidemiological studies indicate that women are at a higher risk developing lung cancer than men are. It is suggested that estrogen is one of the most important factors in lung cancer development in females. Additionally, cigarette smoke, and environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play salient roles in female lung carcinogenesis. However, the mechanism...

Silicosis is an inflammatory lung disease induced by the inhalation of silica-containing dust particles. There is conflicting data on whether patients with silicosis are more susceptible to lung cancer induced by cigarette smoke. To examine this issue experimentally, a model was developed in which one of the most abundant and potent carcinogens present in cigarette smoke [4-(N-methyl-N-nitrosam...

Human CYP2A6 has been recognized as being involved in the mutagenic activation of promutagens such as the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Methoxsalen (8-methoxypsoralen) was reported to inhibit CYP2A6. In the present study, the inhibitory effects of methoxsalen on NNK-induced lung tumorigenesis in female A/J mice were examined. Female A/J mice...

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 phosphate-generating system, metabolites resulting from alpha-hydroxylation, carbonyl reduction,...

To determine whether tobacco-derived carcinogens affect colon carcinogenesis, the effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on colon carcinogenesis were examined using an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. NNK (10 micromol) was administered to male A/J mice by a single intraperitoneal (i.p.) injection and then AOM (10 mg/kg body weight, i.p.) was ...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with T...

An automated in-tube solid-phase microextraction (SPME) HPLC analysis method for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and several metabolites has been developed. NNK is one of the tobacco-specific N-nitrosamines (TSNA), which has been linked to cancers associated with the use of or exposure to tobacco products. In-tube SPME is an on-line extraction technique in which analytes ar...

Lung cancer is the leading cause of cancer death and has a strong etiological association with cigarette smoking. Nicotine and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are two major components in cigarette smoke that significantly contribute to the development of human lung cancer. Nicotine is able to stimulate survival of both normal human lung epithelial and lung cance...