• Title/Summary/Keyword: N-nitrosamine

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Effects of Addition of Precursor and Inhibitor on Formation of N-nitrosamines During Kimchi Fermentation (니트로스아민의 전구 및 억제물질 첨가가 김치 숙성중 니트로스아민의 생성에 미치는 영향)

  • 김준환;신효선
    • Journal of Food Hygiene and Safety
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    • v.13 no.3
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    • pp.274-277
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    • 1998
  • The study was focused to investigate the effect of nitrosodimethylamine (NDMA) formation due to nitrosamine (NA) precursor and/or inhibitor addition to Kimchi during the fermentation of Kimchi at room temperature ($16{\pm}2^{\circ}C$). The addition of nitrite and dimethylamine (DMA) to Kimchi showed the average 32-fold ($21.3{\sim}113.9\;\mu\textrm{g}/kg$) and 9-fold ($1.3{\sim}40.3\;\mu\textrm{g}/kg$) higher NDMA formation than control ($O{\sim}5.6\;\mu\textrm{g}/kg$), respectively. Also, the addition of both nitrite and DMA resulted in the increase of NDMA formation to average 42-fold ($39.4{\sim}155.7\;\mu\textrm{g}/kg$) higher than control. On the other hand, the addition of 4 ruM ascorbic acid to Kimchi with nitrite and DMA inhibited the formation of NDMA down to 71.3% of control. However, the addition of cysteine and erythorbic acid affected no inhibition to NDMA formation during the test. The addition of sodium sulfite increased NDMA formation. Accordingly, this showed that the amount of ascorbic acid generated during Kimchi fermentation played an important inhibition role for NA formation.

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4-(N-Methyl-N-nitrosamino)-1(3-pyridyl)-1-butanone(NNK) Restored the Cap-dependent Protein Translation Blocked by Rapamycin

  • Kim Jun-Sung;Park Jin Hong;Park Sung-Jin;Kim Hyun Woo;Hua Jin;Cho Hyun Sun;Hwang Soon Kyung;Chang Seung Hee;Tehrani Arash Minai;Cho Myung Haing
    • 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.

Screening of Effective Components from Kale to Inhibit N - Nitrosodimethylamine Formation (케일로부터 N-Nitrosamine 생성을 억제시키는 유효성분의 검색)

  • 정미자;이수정;최선영;성낙주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.2
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    • pp.223-229
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    • 2003
  • An amine rich diet with nitrate was incubated in simulated saliva, gastric juice, kale juice, and its ascorbate and methanol soluble portions (5, 10, 15 and 30 mL) for 1 hr at 37$^{\circ}C$ and N-nitrosodimethylamine (NDMA) was detected in the digestion sample, Kale juice and its ascorbate and methanol soluble portions at 30mL inhibited NDMA formation by 60.1$\pm$4.4%, 49.3$\pm$1.2% and 50.1$\pm$2.0%, respectively. The methanol soluble portion was further fractionated by preparative-LC (prep-LC). Nitrite-scavenging effects of 7 methanol soluble portion (Kl, K2, K3, K4, K5, K6 and K7) in kale juice were 2.0 ~56.2%. Among seven fractions, K3, K4, K5 and K7 exhibited weakly on nitrite scavenging effect. Fraction Kl and K2 inhibited NDMA formation by 71.0 and 65.5%, respectively. Fraction Kl and K2 was further separated by prep-LC into 6 subfractions (Kla, Klb, Klc, K2a, K2b and 2nc). Those subfractions inhibited NDMA formation by 40.9 ~80.4%. The K2a subfraction was screened by MS, $^1$H-NMR, $^{13}$ C-NMR and DEPT spectrum.

Elucidation of Dishes High in N-Nitrosamines Using Total Diet Study Data (총식이조사 자료를 이용한 음식별 니트로사민 함량 분포 규명)

  • Choi, Seul Ki;Lee, Youngwon;Seo, Jung-eun;Park, Jong-eun;Lee, Jee-yeon;Kwon, Hoonjeong
    • Journal of Food Hygiene and Safety
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    • v.33 no.5
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    • pp.361-368
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    • 2018
  • N-nitrosamines are probable or possible human carcinogens, which are produced by the reaction between secondary amines and nitrogen oxide in the acidic environment or by heating. Common risk assessment procedure involves the comparison between exposures expressed in the unit, mg/kg body weight/day and the Health-Based Reference dose expressed in the same unit. This procedure is suitable for the policy decision-making and is considered as inappropriate for the consumers to get information about their dietary decision-making. Therefore, the distributions of NDMA (N-nitrosodimethylamine), NDBA (N-nitrosodibutylamine), the six N-nitrosamines (NDMA, NDBA, NDEA (N-nitrosodiethylamine), NPYR (N-nitrosopyrrolidine), NPIP (N-nitrosopiperidine), and NMOR (N-nitrosomorpholine) in the menus grouped based on the presence of main ingredients and cooking methods were analyzed to generate consumer-friendly information regarding food contaminants. Recipes and intakes were taken from 2014 to 2016 KNHANES (The Korean National Health and Nutrition Examination Survey) and only the data from ages of 7 years or older were used. The contamination data were collected from the 2014~2016 Total Diet Study and all the analysis were performed using R software. Rockfish, eel, anchovy broth and pollock were mainly exposed to N-nitrosamines. In terms of cooking methods, soups and stews appeared to contain the highest amount of N-nitrosamines. Cereals, fruits, and dairy products in the ingredient categories, and rice dishes and rice combined with others in recipe categories had the lowest level exposure to N-nitrosamines. In case of N-nitrosamines, unlike other cooking related food contaminants, boiled dishes such as soups and stews and dishes mainly consisting of fishes and shellfishes had highest level of exposure, showing a large discrepancy with the previous thought of processed meat is the main source of N-nitrosamines.

Development of a method for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in dust using liquld chromatography tandem mass spectrometry (LC-MS/MS를 이용하여 먼지 속의 NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) 정량 분석법 개발)

  • Lee, W.K.;Kang, S.J.;Oh, J.E.;Hwang, S.H.;Lee, D.H.
    • Analytical Science and Technology
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    • v.28 no.1
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    • pp.1-7
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    • 2015
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco specific nitrosamine found only in tobacco products. The ability to monitor biomarker concentrations is very important in understanding environmental tobacco smoke (ETS). In this study, an efficient and sensitive method for the analysis of NNK in dust was developed and validated using liquid chromatography tandem mass spectrometry. Dust was collected with filter paper soaked in methanol. The standard solution and dust sample were diluted with 100 mM ammonium acetate and extracted using dichloromethane. Our calibration curves ranged from 25 to $10^4pg/mL$. Excellent linearity was obtained with correlation coefficient values between 0.9996 and 1.0000. The limit of detection (LOD) was 5 pg/mL ($S/N{\geq}3$) and the retention time was 10 min. The limit of quantification (LOQ) was 25 pg/mL, and the acceptance criteria was the rate of 98-103% (80-120% at levels up to $3{\times}LOQ$). The coefficient of variations (CV) was 2.8%. Accuracies determined from dust samples spiked with four different levels of NNK racurves ranged that from 25 to 104 pg/mL. Excellent linearity was obtained between 92.1% and 114%. The precision of the method was acceptable (5% of CV). The recovery rates of the whole analytical procedure at low, medium, and high levels were 105.7-116.5% for NNK. The carry-over effects during LC-MS/MS analysis were not observed for NNK. This manuscript summarizes the scientific evidence on the use of markers to measure ETS.

Diagnosis of fibroadenoma using radiolabeled bladder cancer specific peptide

  • Ha, Yeong Su;Kwak, Wonjung;Lee, Hwa Young;Lee, Byung-Heon;Hong, Il-Hwa;Jeong, Kyu-Shik;An, Gwang Il;Yoo, Jeongsoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.1 no.1
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    • pp.38-45
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    • 2015
  • Most tumors are believed to overexpress several receptors, and small peptides targeting these receptors were developed for diagnosis and tumor therapy during past decade. Here we report that fibroadenoma can be visualized by bladder cancer specific peptide. A 9-mer bladder cancer specific peptide, which was discovered from the phage display method, was synthesized by peptide synthesizer, and additional tyrosine was conjugated at the N-terminal for radioiodination (Y-BP). Y-BP was radiolabeled with $^{131/124}I$ using Iodogen tube. The rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine for 8 weeks was allowed to grow until large size tumor was developed under axilla. The tumor model was microPET imaged sequentially using [$^{18}F$]FDG and radioiodinated $^{124}I-Y-BP$. The tumor was excised and examined by immunostaining studies. Radioiodinated $^{124}I-Y-BP$ was purified using fast protein liquid chromatography (FPLC) in > 90% radiochemical purity. The whole tumor was well visualized by [$^{18}F$]FDG with several intense focal uptake within tumor. The tumor was also clearly seen with $^{124}I-Y-BP$ at 4 h post-injection, and to our surprise the tumor uptake of $^{124}I-Y-BP$ lasted up to three days. The tumor was diagnosed histologically as a fibroadenoma derived from mammary gland. In conclusion, the bladder cancer specific peptide showed the good potential as a new radiotracer for the detection of breast fibroadenoma.

Screening of Effective Factor to Inhibition of NDMA Formation in Yuza (Citrus junos) (유자 중 NDMA 생성억제에 영향을 미치는 인자의 검색)

  • Shin, Jung-Hye;Lee, Jun-Yeal;Cho, Hee-Sook;Lee, Soo-Jung;Jung, Keung-Hee;Sung, Nak-Ju
    • Journal of Food Hygiene and Safety
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    • v.19 no.3
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    • pp.126-131
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    • 2004
  • This study was conducted to investigate of inhibition activity of yuza (Citrus junos) extracts and juice on nitrite scavenging and N-nitrosodimethylamine (NDMA) formation in model system. Yuza juice was separated into organic acid, ascorbate and phenolic portion using sep-pak $C_{18}$ cartridge, respectively. Nitrite scavenging activity and inhibition of NDMA formation from yuza extract has shown higher inhibition with pH of reaction condition lower and amount of added sample more. And peel extract of yuza was higher than those of flesh extract. Nitrite scavenging activity was excellent juice portion rather that 3 portions. Of the 3 portions, it activity was the highest in the organic acid portion, and decreased in the following order; phenolic acid, ascorbate portion. Therefore, organic acid of yuza was suggested to expect effective ihhibitor of NDMA formation.

Effect of Temperature, pH and Salt Concnetration on formation of N-nitrosamines during Kimchi Fermentation (김치숙성중 숙성온도, pH 및 소금 농도가 니트로스아민의 생성에 미치는 영향)

  • 김준환;장영상;신효선
    • Journal of Food Hygiene and Safety
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    • v.13 no.4
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    • pp.332-336
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    • 1998
  • The effect of ripening temperature, pH and salinity on the formation of Nnitrosamine (NA) during Kimchi fermentation and in vitro was studied, respectively. During Kimchi fermentation for six weeks at cold storage temperature ($4^{\circ}C$) and room temperature ($16{\pm}2^{\circ}C$), the contents of nitrite and dimethylamine (DMA) showed variation at room temperature but no variation at cold storage temperature. The maximum generation of nitrosodimethylamine (NDMA) resulted low content ($2.69\;\mu\textrm{g}/kg$) at cold storage temperature but started to increase after one week fermentation and reached to the 18-fold higher generation ($49.6\;\mu\textrm{g}/kg$) at room temperature. During Kimchi fermentation, no correlation was observed between the variation of nitrite and DMA content and the generation of NDMA. However, pH showed effective relation to NDMA generation such as the highest NDMA generation was obtained at lowest pH 4. During in vitro test, higher temperature and lower pH resulted more NDMA generation and generation amount was affected more by pH. Also, the salinity of Kimchi provided inhibitory effects on the formation of NDMA. NDMA was produced $5.86\;\mu\textrm{g}/kg$ at normal salinity (2.5%) but $90.9\;\mu\textrm{g}/kg$ at lower salinity (15%) after three week. The higher salinity showed lower formation of NDMA in vitro test, too.

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Recurrent Early Gastric Cancer with Liver Metastasis Mimicking Pancreaticobiliary Cancer (조기위암으로 위 절제술 후 갑자기 발생한 췌담도암으로 오인되었던 재발성 위암 1례)

  • Byung Hoo Lee;Joo Young Cho
    • Journal of Digestive Cancer Research
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    • v.1 no.1
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    • pp.48-51
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    • 2013
  • We report an unusual case of postoperative early gastric cancer with liver metastasis mimicking pancreaticobiliary carcinoma. A 73-year-old man with early gastric cancer was transferred for endoscopic treatment. The patient underwent endoscopic submucosal dissection for the treatment of the early gastric cancer. The pathological diagnosis was adenocarcinoma with extension to the deep submucosa and some lymphatic invasion. Therefore, subsequent a subtotal gastrectomy was performed. The histological results demonstrated residual adenocarcinoma confined to the mucosa. The resection margin and lymph node metastasis were negative. Thus, he was closely monitored for recurrence every 6 months. After 2 years, he was suddenly suspected of developing liver metastasis and local recurrence. He received a liver biopsy, and the pathological result was poorly differentiated adenocarcinoma. Immunohistochemical staining suggested pancreaticobiliary carcinoma rather than metastatic adenocarcinoma from the stomach or colon, but primary focus was not found. We were sure that the recurrent stomach cancer metastasized to the liver because stomach cancer can show heterogeneous cytokeratin (CK) expression pattern with various histological features. Therefore, no single CK expression pattern has diagnostic value for distinguishing gastric carcinoma. The patient underwent chemotherapy for metastatic stomach cancer.

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Inhibitory Action of Natural Food Components on the Formation of Carcinogenic Nitrosamine (천연식품성분에 의한 발암성 니트로사민의 생성억제작용)

  • AHN Bang-Weon;LEE Dong-Ho;YEO Saeng-Gyu;KANG Jin-Hoon;DO Jeong-Ryong;KIM Seon-Bong;PARK Yeung-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.26 no.4
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    • pp.289-295
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    • 1993
  • The present paper was investigated in the inhibitory action of vegetable and seaweed water-soluble extracts on the formation of carcinogenic N-nitrosodimethylamine(NDMA). The vegetable and seaweed extracts obtained from garlic(Allium sativum), onion(Allium cepa), green onion(Allium fistuiosum), chinese pepper(Fagara mandshurica), green pepper(Capsicum annuum), red pepper(Capsicum annuum), ginger(Zingiber officinale), carrot(Daucus carota), laver(Porphyra tenera), sea lettuce(Entero compresa), sea mustard(Undaria pinnatifida) and sea staghorn(Codium fragile) were incubated with sodium nitrite-dimethylamine mixtures at $37^{\circ}C$ under different pH conditions The formation of NDMA was reduced to $10{\sim}40\%\;and\;25{\sim}50\%$ by the addition of vegetable and seaweed extracts 30mg at pH 1.2, respectively. The inhibition degree by the extracts at pH 1.2 was similiar to that at pH 4.2 and to that by ascorbic acid at pH 1.2. The inhibitory action of the extracts against NDMA formation was not decreased by heat treatment at $80^{\circ}C$ for 10min, but decreased by the treatment of sodium borohydride. It is assumed that reducing powers of the extracts participated in their inhibitory actions.

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