• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2207-2212
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• 2012

Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of $RAR{\beta}$. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor ${\beta}$($RAR{\beta}$). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of $RAR{\beta}$ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het-1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of $RAR{\beta}$ in esophageal SCC patients. NNK could induce $RAR{\beta}$ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.

• Toxicological Research
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• v.21 no.4
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• pp.347-353
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• 2005

Eukaryotic initiation factor 4E (elF4E) is a key element for cap-dependent protein translation controlled by affinity between elF4E and 4E-binding protein 1 (4E-BP1). Rapamycin can also affect protein translation by regulating 4E-BP1 phosphorylation. Tobacco-specific nitrosamine, 4(N-methyl-N-nitrosamino )-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen, but its precise lung cancer induction mechanism remains unknown. Relative roles of cap-dependent and -independent protein translation in terms of NNK-induced lung carcinogenesis were elucidated using normal human bronchial epithelial cells. NNK concentrations applied in this study did not decrease cell viability. Addition of NNK restored rapamycin-induced decrease of protein synthesis and rapamycin-induced phosphorylation of 4E-BP1, and increased expression levels of mTOR, ERK1/2, p70S6K, and Raf-1 in a concentration-dependent manner. NNK also caused perturbation of normal cell cycle progression. Taken together, NNK might cause toxicity through the combination of restoration of 4E-BP1 phosphorylation and increase of elF4E as well as mTOR protein expression, interruption of Raf1/ERK as well as the cyclin G-associated p53 network. Our data could be applied towards elucidation of the molecular basis for lung cancer treatment.

• Environmental Mutagens and Carcinogens
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• v.25 no.3
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• pp.118-123
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• 2005

Nicotine has been implicated as a potential factor in the pathogenesis of human lung cancer, however its mechanism of action in the development of lung cancer remains largely unknown. To explore the role of nicotine in the development of lung cancer, we first investigated the effects of nicotine on the expression of tumor associated genes by treating Sprague-Dawley rats with nicotine (10 mg/kg) by gavage once daily for 10 days. We determined the expression of proteins and mRNAs of the ras, raf, myc, jun, fos oncogenes and p53, Rb tumor suppressor genes by Western and Northern blotting, respectively. We did not detect any changes on the levels of proteins and mRNAs of these tumor associated genes in the lung of Sprague-Dawley rats from 3 days to 12 weeks after the last treatment of nicotine, indicating that nicotine appears to have no effect on expression of these oncogenes and tumor suppressor genes at an early stage in multistage chemical carcinogenesis. In a second experiment, we investigated the possibility that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could be formed endogenously by treating with nicotine and sodium nitrite. We treated groups of Fischer 344 rats with nicotine ($60{\mu}mol/kg$) and sodium nitrite ($180{\mu}mol/kg$), nicotine, sodium nitrite and NNK (120 nmol/kg) alone by gavage once daily for 7 days, respectively and determined the 8-hydroxydeoxyguanosine (8-OHdG), as an indicator of NNK formation, in the lungs of rats 24 hours and 48 hours after the last treatment by HPLC/ECD method. We detect increased level of 8-OHdG in the lungs of rats treated with NNK, but in the case of nicotine plus sodium nitrite, nicotine and sodium nitrite alone we could not detected any changes of 8-OHdG, respectively.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.7
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• pp.974-980
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• 2014

In semi-arid areas of Southern Africa, dehydration can compromise the performance and welfare of local chickens, particularly during the growing period when confinement is curtailed and birds are left to scavenge for feed and water. The effect of water restriction on the growth performance was compared in Naked Neck (NNK) and Ovambo (OVB) chickens that are predominant in Southern Africa. A total of 54 eight-wk-old pullets each of NNK and OVB chickens with an initial average weight of $641{\pm}10g/bird$ were randomly assigned to three water intake treatments, each having six birds for 8 wk. The water restriction treatments were ad libitum, 70% of ad libitum and 40% of ad libitum intake. Nine experimental pens with a floor space of $3.3m^2$ per strain were used. The pens were housed in an open-sided house with cement floor deep littered with a 20 cm layer of untreated wood shavings. Feed was provided ad libitum. Average daily water intake (ADWI), BW at 16 weeks of age (FBW), ADG, ADFI, feed conversion ratio (FCR) and water to feed ratios (WFR) were determined. Ovambo chickens had superior (p<0.05) FBW, ADG and ADWI than NNK chickens. Body weight of birds at 16 weeks of age, ADG, ADFI, ADWI, and WFR declined progressively (p<0.05) with increasing severity of water restriction while FCR values increased (p<0.05) as the severity of water restriction increased. Naked Neck chickens had better FCR at the 40% of ad libitum water intake level than Ovambo chickens. The dressing percentage per bird was higher in water restricted birds than those on ad libitum water consumption, irrespective of strain. Heart weight was significantly lower in birds on 40% of ad libitum water intake than those on ad libitum and 70% of ad libitum water intake, respectively. In conclusion, NNK chickens performed better than OVB chickens under conditions of water restriction and would be ideal to raise for meat and egg production in locations where water shortages are a major challenge.

• Membrane and Water Treatment
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• v.8 no.3
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• pp.245-257
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• 2017

The separation of nicotine and tobacco-specific N-nitrosamines is a tough problem in tobacco industry. In this study, separation of nicotine from 4-(methylnitrosamino) -1-(3-pyridyl)-1-butanone (NNK) mixtures was investigated using electrodialysis by taking the principle of the protonation status difference between these two components. The results indicated that the solution pH has a dominant impact on the separation process. In a pH range of 5-7, nicotine molecules are existed as mono- and di-protonated ions and can be separated from the uncharged NNK molecules. The acidic electrolyte is conducive to the separation process from the point of flux and energy consumption; while the alkaline electrolyte has negative impact on the separation process. A current density of $10mA/cm^2$ is an appropriate value for the separation process. The lowest energy consumption of the separation process is 0.58 kWh/kg nicotine with the process cost to be estimated at only $0.208 /kg nicotine. Naturally, electrodialysis is a high-efficiency, cost-effective, and environmentally friendly process to separate and purify nicotine from tobacco juice.

• Advanced Composite Materials
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• v.18 no.3
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• pp.233-249
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• 2009

Safe installation and operation of high-pressure composite cylinders for hydrogen storage are of primary concern. It is unavoidable for the cylinders to experience temperature variation and significant thermal input during service. The maximum failure pressure that the cylinder can sustain is affected due to the dependence of composite material properties on temperature and complexity of cylinder design. Most of the analysis reported for high-pressure composite cylinders is based on simplifying assumptions and does not account for complexities like thermo-mechanical behavior and temperature dependent material properties. In the present work, a comprehensive finite element simulation tool for the design of hydrogen storage cylinder system is developed. The structural response of the cylinder is analyzed using laminated shell theory accounting for transverse shear deformation and geometric nonlinearity. A composite failure model is used to evaluate the failure pressure under various thermo-mechanical loadings. A back-propagation neural network (NNk) model is developed to predict the maximum failure pressure using the analysis results. The failure pressures predicted from NNk model are compared with those from test cases. The developed NNk model is capable of predicting the failure pressure for any given loading condition.

• 대한치주과학회:학술대회논문집
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• 1998.11a
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• pp.32-32
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• 1998

• 대한치주과학회:학술대회논문집
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• 1998.11a
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• pp.95-95
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• 1998

• Journal of Environmental Health Sciences
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• v.40 no.1
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• pp.10-16
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• 2014

Objectives: This pilot study assessed secondhand smoke (SHS) exposure in smoking and non-smoking nightclubs in Seoul, Korea by measuring the concentration of particulate matter smaller than $2.5{\mu}m$ ($PM_{2.5}$). Methods: This comparative study was conducted in three nightclubs in Seoul. While one non-smoking nightclub was measured on weekdays and weekends, different smoking nightclubs were measured on weekdays and weekends. The concentration of $PM_{2.5}$ was observed using a real-time monitor over an average of three hours. The number of people in the clubs was also estimated. Settled dust was collected in a smoking and a non-smoking nightclub and analyzed for NNK concentration. Results: The $PM_{2.5}$ concentration in the smoking nightclubs was higher than those found in the non-smoking nightclub by 26 times on weekdays and three times on weekends. Indoor $PM_{2.5}$ concentration was correlated with the number of people in the smoking nightclubs. Relatively high $PM_{2.5}$ concentration was observed in the non-smoking nightclub on weekends. NNK concentration in the smoking nightclub was 7 times higer than in the non-smoking nightclub. Conclusion: Smoking in nightclubs caused high $PM_{2.5}$ concentration. Although the non-smoking nightclub had a lower $PM_{2.5}$ concentration, $PM_{2.5}$ concentration on weekends was higher due to the smoking room. Complete prohibition of smoking in nightclubs can protect patrons from secondhand smoke exposure.

• Korean Journal of Environmental Agriculture
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• v.19 no.2
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• pp.147-153
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• 2000

Cigarette smoking deals a harmful effect directly to smokers and even to non-smokers through environmental tobacco smoke. The major damaging component in cigarette smoke is nicotine which converts to various carcinogens. Among the carcinogenic metabolites, nitrosamine-4-(methylnitrosamino)-1- (3-pyridyl)-1- butanone (NNK) is responsible for many types of lung cancers. Recent studies report that activation of NNK is markedly inhibited in the presence of cotinine, a safer metabolite from nicotine. It is well known that tea extract have potentials to prevent cancers. This study aims to correlate green tea's potential for cancer prevention with an accelerated formation of cotinine. In the presence of tea extract, a nicotine to cotinine conversion was studied in established cell lines and xenopus oocytes. Among three lines of cell used, PLC/PRF5 and 293 cells showed a fast turnover from nicotine to cotinine while HepG2 cell line showed a marginal difference between groups treated and non-treated with tea extract. A microinjection procedure using Xenopus oocyte was utilized to probe for the effect of tea extract in accelerating nicotine conversion to cotinine. According to this procedure, tea extract's unusual potential for converting nicotine to cotinine is also substantiated. Overall, this present study indicated that tea extract have an unusual effect on conversion of nicotine to cotinine in cells.