1.The NAD(P)H: quinone oxidoreductase 1 C609T polymorphism and susceptibility to esophageal cancer.
Jian-hui ZHANG ; Yan LI ; Rui WANG ; Mario SARBIA ; Wei GUO ; Deng-gui WEN ; Li-zhen WEI ; Zhi-feng CHEN ; Gang KUANG ; Li-wei ZHANG ; Ming HE ; Ming-li WU ; Shi-jie WANG
Chinese Journal of Medical Genetics 2003;20(6):544-546
<p>OBJECTIVETo investigate the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a northern Chinese population.p><p>METHODSThe NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis in 193 patients with ESCC and 141 unrelated healthy controls.p><p>RESULTSThe frequency of the T allele (null) among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.86, P=0.028). The NQO1 C/C and C/T genotype distribution among ESCC patients was not significantly different from that among healthy controls (Chi-square= 2.27 and 0.127; P=0.132 and 0.721, respectively). However, the T/T genotype frequency among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.39, P=0.036). The NQO1 T/T genotype significantly increased the risk for developing ESCC, compared to the combination of C/C and C/T genotypes, with the adjusted odds ratio (OR) of 1.81 (95%CI: 1.04-3.15). This increased susceptibility exhibited pronouncedly in patients with family history of upper gastrointestinal cancers (adjusted OR=2.22, 95%CI 1.18-4.17).p><p>CONCLUSIONDetermination of the NQO1 C609T genotype may be used as a stratification marker to predicate high-risk individuals for ESCC.p>
Esophageal Neoplasms
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genetics
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Genetic Predisposition to Disease
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Genotype
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Humans
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NAD(P)H Dehydrogenase (Quinone)
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genetics
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Polymorphism, Genetic
2.The Growth Inhibitory Effects of Atrina Pecitinata Fractions on Cancer Cell Lines.
Soung Young PARK ; Mi Ok SHIN ; Sang Hyun LEE ; Song Ja BAE
The Korean Journal of Nutrition 2005;38(4):307-312
We investigated the growth inhibitory effects of Atrina pecitinata (AP) on the proliferation in human cancer cell lines in vitro. AP was extracted with methanol which was further fractionated into four diffferent types: methanol (APMM), haxane (APMH), butanol (APMB), and aquous layers (APMA). Among various partition layers, the APMM showed the strongest cytotoxic effects on all cancer cell lines which we used. In the MTT assay of AP fractions, the growth inhibitory effects was increased in proportion to its concentration. We observed quinone reductase (QR) induced effects in all fraction layers of AP on HepG2 cells. The QR induced effects of APMM on HepG2 cell at 80 microgram/mL concentration indicated 2.0 with a control value of 1.0.
Cell Line*
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Hep G2 Cells
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Humans
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Methanol
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NAD(P)H Dehydrogenase (Quinone)
3.The Effects on Antimicrobial and Cytotoxicity of Hijikia Fusiformis Fraction.
Jae Hak SHON ; Dae Yeon KANG ; Hyun Cheol OH ; Bok Mi JUNG ; Mi Hyang KIM ; Mi Ok SHIN ; Song Ja BAE
The Korean Journal of Nutrition 2006;39(5):444-450
In this study, we investigated antimicrobial and cytotoxicity effects to each fraction extracted from Hizikia fusiformis (HF), which were extracted methanol (HFM)and then the extract was fractionated into four different types: hexane (HFMH), methanol (HFMM), butanol (HFMB) and aquous (HFMA) partition layers. We determined the cytotoxic effect of these layers on human cancer cells by MTT assay. Among various partition layers of HF, the HFMB and HFMM were showed the strong cytotoxic effects on cancer cell lines we used. The quinone reductase (QR) induced activity of the HFMB on HepG2 cells at 150 microgram/mL concentration was 2.63 times more effective compared to the control value of 1.0. Although further studies are needed, the present work suggests that HF maybe a chemopreventive agent for the treatment of human cancer cells.
Cell Line
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Hep G2 Cells
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Humans
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Methanol
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NAD(P)H Dehydrogenase (Quinone)
5.Cytotoxicity and Quinone Reductase Activity Stimulating Effects of Fin of Thunnus Thynnus Extracts in Various Cancer Cells.
Mi Ok SHIN ; Mi Jeong KU ; Song Ja BAE
The Korean Journal of Nutrition 2007;40(2):147-153
In this study, we investigated the anticancer activity of the fin of Thunnus Thynnus (TT ). TT was extracted with methanol (TTM ), and then further fractionated into four subfractions by using solvent partition method, affording hexane (TTMH ), methanol (TTMM ), butanol (TTMB )and aquous (TTMA )soluble fractions. We determined the cyto-toxicity of these four fractions in four kind of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. The TTMM showed the strongest cytotoxic effect at the concentration of 150 microgram/mL, displaying 95% on the HepG2 cell lines and 82% on MCF-7 cell line. The morphological changes such as membrane shirinking and blebbing of cells were also observed by TTMM treatment in HT29 cell. In addition, we observed that quinone reductase (QR ) activity was elevated by only TTMM and TTMH treatments in HepG2 cell. QR activity was increased to around 2.0 and 1.8 times in TTMM and TTMH treated HepG2 cell at 100 microgram/mL, respectively, compared to that in control. Although further studies are needed, the present work could suggest that the fin of TT has a potential to be usable as a chemo-preventive agent against cancer.
Blister
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Cell Line
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Hep G2 Cells
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HT29 Cells
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Humans
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MCF-7 Cells
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Membranes
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Methanol
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NAD(P)H Dehydrogenase (Quinone)*
6.Effect of Chitosan Oligosaccharide on Enzymes for Cancer Chemoprevention.
To Hun KIM ; Young Jung JO ; Young Min HA ; Yun Hee SHON ; Byung Jo BAE ; Kyung Soo NAM
Journal of the Korean Cancer Association 2001;33(1):64-70
PURPOSE: Two types of chitosan oligosaccharides (COSs), COS I and COS II, were investigated for the effects on ascitic tumor and enzymes for cancer chemoprevention. MATERIALS AND METHODS: Chitosan oligosaccharides were administered once daily for 10 days after the tumor implantation. The change of body weight was observed for 20 days, and the survival rate of mice was determined after 21 days. Chitosan oligosaccharides were administered once daily for 10 days before the tumor implantation (1 106 cells). The number of ascitic tumor cells were measured at 6 days after tumor implantation. Chemopreventive potential of chitosan oligosaccharides was examined by the induction of quinone reductase and inhibition of cytochrome P450 1A1. RESULTS: Chitosan oligosaccharides exerted antitumor activity by inhibiting the growth of Ehrlich ascites tumor cells in vivo. Mice given Ehrlich cells and 10 or 100 mg/kg body weight of chitosan oligosaccharides had 33% survival after 21 days. Quinone reductase activity was increased with chitosan oligosaccharides. There were 26% and 33% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of COS I and COS II, respectively. CONCLUSION: These results suggest that chitosan oligosaccharides has antitumor activity and cancer chemo preventive potential by inducing QR activity and inhibiting cytochrome P450 1A1.
Animals
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Body Weight
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Carcinoma, Ehrlich Tumor
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Chemoprevention*
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Chitosan*
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Cytochrome P-450 Enzyme System
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Mice
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NAD(P)H Dehydrogenase (Quinone)
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Oligosaccharides
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Survival Rate
7.Inactivation of Aconitase by Tetrahydrobiopterin in DArgic Cells: Relevance to PD.
Nam Soo YOON ; Yuri CHO ; So Yeon LEE ; Hyun Jin CHOI ; Onyou HWANG
Experimental Neurobiology 2010;19(1):23-29
Oxidative damage is thought to be a major cause of the progression of dopamine (DA)rgic neurodegeneration as in Parkinson's disease. We have previously reported that tetrahydrobiopterin (BH4), an endogenous molecule required for DA synthesis, exerts oxidative stress to DA-producing cells and facilitates the production of DA quinone. It is known that aconitase, present in both mitochondrial and cytosolic forms, act as an reactive oxygen species (ROS) sensor, and that their inactivation leads to further generation of ROS. In the present study we investigated whether the BH4-associated vulnerability of DA cells might involve aconitase. In DArgic cell line CATH.a, BH4 treatment caused reduction of activity of both mitochondrial and cytosolic aconitases, and this appeared to be due to direct inactivation of the pre-existing enzyme molecules. Although most of the activity reduced by BH4 was increased upon reactivation reaction under a reducing condition, the restoration was not complete, suggesting that irreversible and covalent modification has occurred. The aconitase inactivation was exacerbated in the presence of DA and attenuated in the presence of tyrosine hydroxylase inhibitor a-methyl-p-tyrosine, suggesting the involvement of DA. The degree of inactivation increased when the cells were treated with the quinone reductase inhibitor dicoumarol and decreased in the presence of quinone reductase inducer sulforaphane. Taken together, BH4 appeared to lead to both reversible and irreversible inactivation of aconitase and that this is facilitated by the presence of DA and accumulation of DA quinone.
Aconitate Hydratase
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Benzoquinones
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Biopterin
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Cell Line
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Cytosol
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Dicumarol
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Dopamine
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NAD(P)H Dehydrogenase (Quinone)
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Oxidative Stress
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Parkinson Disease
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Reactive Oxygen Species
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Thiocyanates
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Tyrosine 3-Monooxygenase
8.Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity.
Ji Yeon SEO ; Soon Sung LIM ; Jia PARK ; Ji Sun LIM ; Hyo Jung KIM ; Hui Jung KANG ; Jung Han YOON PARK ; Jong Sang KIM
Nutrition Research and Practice 2010;4(2):93-98
Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by CCl4 treatment to the control level. Hepatic injury induced by CCl4 was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by CCl4.
Alkanes
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Animals
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Antioxidant Response Elements
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Carbon
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Carbon Tetrachloride
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Chrysanthemum
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Glutathione Transferase
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Kidney
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Liver
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Luciferases
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Methanol
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Mice
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NAD(P)H Dehydrogenase (Quinone)
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Stomach
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Transcriptional Activation
10.Genetic polymorphisms of NQO1, GSTT1, GSTM1 and susceptibility to chronic benzene poisoning.
Yan CHEN ; Gui-lan LI ; Zhi-ying JI ; Jian-ning XU ; Chun-Ling WU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(1):1-5
<p>OBJECTIVETo explore the relationship between genetic polymorphism of quinone oxidoreductase 1 (NQO1), glutathione S-transferase theta 1 (GSTT1), glutathiones S-transferase mu 1 (GSTM1) and susceptibility to chronic benzene poisoning (BP).p><p>METHODSThe genotypes of NQO1, GSTT1, GSTM1 for 100 patients with benzene poisoning and 90 workers exposed to benzene who were engaged in the same working time and job title as patients with benzene poisoning were detected by PCR-RFLP and multi-PCR.p><p>RESULTSThere was a 2.82-fold (95% CI: 1.42 approximately 5.58, P < 0.05) increased risk of BP in the subjects with NQO1 C609T mutation genotype (T/T) compared with those carrying heterozygous (C/T) and wild type (C/C), and there was a 2.94-fold (95% CI: 1.25 approximately 6.90, P < 0.05) increased risk of BP in the subjects with NQO1 C609T T/T genotype compared with those carrying C/C genotype. The subjects with GSTT1 null genotype had a 1.91-fold (95% CI: 1.05 approximately 3.45, P < 0.05) increased risk of BP compared with those with GSTT1 non-null genotype. The interaction of two genes showed that there was a increased risk of BP in subjects with any two genotypes of NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype, compared to the individual with any two genotypes of NQO1 C609T C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype. The interaction of three genes showed that there was a 20.41-fold (95% CI: 3.79 approximately 111.11, P < 0.01) increased risk of BP in subjects with NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype compared with those carrying NQO1 C609T C/T genotype and C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype.p><p>CONCLUSIONSThe interaction of multi-genes may be an important role to BP. The genetic polymorphisms of 3 genes (NQO1, GSTT1 and GSTM1) led to declining of detoxifying ability in benzene metabolism, so the individual with NQO1 C609T T/T genotype, GSTT1 null genotype and GSTM1 null genotype is most susceptive to benzene. The results were consistent with that of the theoretic presumption. It could be suggested as a biomarker to assess the risk of benzene poisoning for individuals.p>
Adult
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Aged
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Benzene
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poisoning
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Case-Control Studies
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Chronic Disease
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Female
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Genetic Predisposition to Disease
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Glutathione Transferase
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genetics
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Humans
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Male
;
Middle Aged
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NAD(P)H Dehydrogenase (Quinone)
;
genetics
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Polymorphism, Genetic