• Title/Summary/Keyword: N-acetyltransferase

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Urinary Bladder Cancer Risk Factors: A Lebanese Case-Control Study

  • Kobeissi, Loulou Hassan;Yassine, Ibrahim Adnan;Jabbour, Michel Elias;Moussa, Mohamad Ahmad;Dhaini, Hassan Rida
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3205-3211
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    • 2013
  • Background: Bladder cancer is the second most incident malignancy among Lebanese men. The purpose of this study was to investigate potential risk factors associated with this observed high incidence. Methods: A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently selected from the same settings. Data were collected using interview questionnaire and blood analysis. Exposure data were collected using a structured face-to-face interview questionnaire. Blood samples were collected to determine N-acetyltransferase1 (NAT1) genotype by PCR-RFLP. Analyses revolved around univariate, bivariate and multivariate logistic regression, along with checks for effect modification. Results: The odds of having bladder cancer among smokers was 1.02 times significantly higher in cases vs. controls. The odds of exposure to occupational diesel or fuel combustion fumes were 4.1 times significantly higher in cases vs controls. The odds of prostate-related morbidity were 5.6 times significantly higher in cases vs controls. Cases and controls showed different clustering patterns of NAT1 alleles. No significant differences between cases and controls were found for consumption of alcohol, coffee, tea, or artificial sweeteners. Conclusions: This is the first case-control study investigating bladder cancer risk factors in the Lebanese context. Results confirmed established risk factors in the literature, particularly smoking and occupational exposure to diesel. The herein observed associations should be used to develop appropriate prevention policies and intervention strategies, in order to control this alarming disease in Lebanon.

Increased Expression of aac(3)II by Tn3 in Gentamicin - Resistant Bacteria Isolated from Hospital Sewage (병원하수로부터 분리한 Gentamicin 저항성 세균에서 Tn3에 의한 aac(3)II의 발현 증가)

  • 한효심;이문숙;정재성
    • Korean Journal of Microbiology
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    • v.40 no.1
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    • pp.60-64
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    • 2004
  • We tested gentamicin - resistant bacteria isolated from hospital sewage to confirm the presence of aac(3)II encoding aminoglycoside- (3)-N- acetyltransferase by dot-blot hybridization. A probe from the internal fragment of aac(3)II was hybridized to DNA from 41 % (39/95) of gentamicin resistant isolates. PCR was performed with primers from aac(3)II and Tn3. Of 39 strains, 13 strains had Tn3-aac(3)II structure. Minimal inhibitory concentration (MIC) test demonstrated that 18 strains containing Tn3-aac(3)II showed higher resistance to gentamicin than those of other strains. Thirteen strains were identified as 5 Escherichia coli, 3 Acinetobacter johnsonii, 2 Enterobacter agglomerans, 2 Micrococcus luteus, and 1 Pseudomonas facilis. These results suggest that gentamicin-resistant determinant of Tn3-aac(3)II structure was widely distributed in the gentamicin-resistant bacteria.

Association of Genetic Polymorphism of Glutathione S-transferase M1, T1 and N-acetyltransferase 1 with Lung Cancer (폐암발생과 Glutathione S-transferase M1, T1 및 N-acetyltransferase 1의 유전적 다형성과의 연관성에 관한 연구)

  • Lee, Seung-Joon;Park, Gye-Young;Oh, Yeon-Mok;Kang, Dae-Hee;Cho, Soo-Hun;Kim, Soo-Ung;Yoo, Chul-Gyu;Lee, Chun-Taeck;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.4
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    • pp.471-477
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    • 1999
  • Background : Smoking and high-risk occupation have been known to be the risk factors of lung cancer. The carcinogen-metabolizing enzymes in human body such as glutathione S-transferase M1, T1 and N-acetyltransferase 1 have also been regarded as risk factors in many cancers, because the activities of those enzymes play a role in metabolizing the carcinogen. A case-control study was conducted to evaluate the genetic polymorphism of GSTM1, T1 and NAT1 in lung carcinogenesis in Korean men. Methods : The histologically proven lung cancer cases were recruited from Seoul National University Hospital. The patients of more than 40-year-old with the nonmalignant urinary tract diseases were recruited as controls from the same hospitals. The informations of demographical characteristics and smoking were obtained by interview or chart review and the genetic polymorphisms of GSTM1, T1 and NAT1 were determined by PCR-based assay. The statistical analyses were performed by linear logistic regression. Results : The number of case-control was 118 and 150, respectively. The smoking history was significantly higher in the lung cancer patients than the controls. The prevalence of GSTM1 null-type was statistically higher(OR=2.25 ; 95% CI=1.12-4.51) in squamous cell carcinoma than other genotypes, but other histologic types were not The prevalence of GSTT1 null-type were not statistically higher than other genotypes in all histologic types. The fast acetylator of NAT1 was more prevalent than normal(OR=2.13 ; 95% CI=1.04-4.40) in all lung cancer patients. Conclusion : The null-type of GSTM1 and fast acetylator of NAT1 are associated with development of lung cancer in Korean men.

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The Ribostamycin Biosynthetic Gene Cluster in Streptomyces ribosidificus: Comparison with Butirosin Biosynthesis

  • Subba, Bimala;Kharel, Madan Kumar;Lee, Hei Chan;Liou, Kwangkyoung;Kim, Byung-Gee;Sohng, Jae Kyung
    • Molecules and Cells
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    • v.20 no.1
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    • pp.90-96
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    • 2005
  • A cluster of genes for ribostamycin (Rbm) biosynthesis was isolated from Streptomyces ribosidificus ATCC 21294. Sequencing of 31.892 kb of the genomic DNA of S. ribosidificus revealed 26 open reading frames (ORFs) encoding putative Rbm biosynthetic genes as well as resistance and other genes. One of ten putative Rbm biosynthetic genes, rbmA, was expressed in S. lividans TK24, and shown to encode 2-deoxy-scyllo-inosose (DOI) synthase. Acetylation of various aminoglycoside-aminocyclitol (AmAcs) by RbmI confirmed it to be an aminoglycoside 3-N-acetyltransferase. Comparison of the genetic control of ribostamycin and butirosin biosynthesis pointed to a common biosynthetic route for these compounds, despite the considerable differences between them in genetic organization.

Human Cytochrome P450 Metabolic Activation in Chemical Toxicity

  • Kim, Dong-Hak;Chun, Young-Jin
    • Toxicological Research
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    • v.23 no.3
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    • pp.189-196
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    • 2007
  • Cytochrome P450 (P450) enzymes are the major catalysts involved in the biotransformation of various drugs, pollutants, carcinogens, and many endogenous compounds. Most of chemical carcinogens are not active by themselves but they require metabolic activation. P450 isozymes playa pivotal role in the metabolic activation. The activation of arylamines and heterocyclic arylamines (HAAs) involves critical N-hydroxylation, usually by P450. CYP1A2 plays an important role in these reactions. Broad exposure to many of these compounds might cause carcinogenicity in animals and humans. On the other hand, P450s can be also involved in the bioactivation of other chemicals including alcohols, aflatoxin B1, acetaminophen, and trichloroethylene, both in humans and in experimental animals. Understanding the P450 metabolic activation of many chemicals is necessary to develop rational strategies for prevention of their toxicities in human health. An important part is the issues of extrapolation between species in predicting risks and variation of P450 enzyme activities in humans.

Effects of Exercise Preconditioning on the Expression of NGF, Synapsin I, and ChAT in the Hippocampus of Socially Isolated Rats (사회적으로 고립된 쥐의 해마에서 NGF와 Synapsin I, ChAT의 단백질 수준에 미치는 사전운동효과)

  • Hong, Young-Pyo;Kim, Hyun-Tae
    • Journal of Life Science
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    • v.22 no.9
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    • pp.1180-1186
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    • 2012
  • The purpose of this study was to investigate the effect of exercise preconditioning (EPC) on nerve growth factor (NGF), synapsin I, and choline acetyltransferase (ChAT) in the hippocampus of rats subjected to social isolation (SI). We randomly assigned four groups of male Sprague-Dawley (SD) rats (n=32) to the following treatments: GC: group housing control; IC: isolation control; GE: group housing exercise; IE: isolation exercise (n=8 each group). The rats underwent EPC 5 days a week for 8 weeks, and the speed of the treadmill was gradually increased (grade $0^{\circ}C$). After EPC, they were immediately subjected to SI for 8 weeks. The results showed that the protein levels of NGF, synapsin I, and ChAT in the hippocampus were significantly decreased in the IC group (p<0.05) compared with the GC group. However, these protein levels were significantly higher in the IE group (p<0.05). These results show that EPC may buffer the decline of function in the hippocampus by ameliorating the reduction in NGF, synapsin I, and ChAT induced by SI.

A case-control study on the effects of the genetic polymorphisms of N-acetyltransferase 2 and glutathione S-transferase mu and theta on the risk of bladder cancer (N-Acetyltransferase 2와 glutathione S-transferase mu 및 theta 다형성이 방광암 발생에 미치는 영향에 대한 환자-대조군 연구)

  • Kim, Heon;Kim, Wun-Jae;Lee, Hyung-Lae;Lee, Moo-Song;Kim, Cheol-Hwan;Kim, Ro-Sa;Nan, Hong-Mei
    • Journal of Preventive Medicine and Public Health
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    • v.31 no.2 s.61
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    • pp.275-284
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    • 1998
  • Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which .educe the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTMI) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% to. the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity($\chi^2_{trend}=1.18$, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls ($\chi^2=5.21$, P-value<0.05), and the odds ratio (95% CI) was 2.23 (1.12 - 4.56). GSTT1 deletion, the .ate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history turned out to be insignificant as a risk factor of bladder cancer (OR=1.85, 95% CI: 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR: 2.56, 95% CI: 1.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.

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Changes in Body Growth and Growth-Related Genes under Different Photoperiods in Olive Flounder, Paralichthys olivaceus

  • Kim, Byeong-Hoon;Lee, Chi-Hoon;Choi, Song-Hee;Lee, Young-Don
    • Development and Reproduction
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    • v.23 no.2
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    • pp.149-160
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    • 2019
  • This study examined the effects of different photoperiod conditions on olive flounder (Paralichthys olivaceus), a commercially important species in Korea. Daily variations in the expression of mRNA for the growth-related genes arylalkylamine N-acetyltransferase2 (AANAT2), preprosomatostatin1 (PSS1), and growth hormone (GH) were examined under a 12 h light:12 h dark photoperiod. All the genes were expressed at higher level during the dark period. Melatonin injections increased the expression of GH, but did not significantly affect the expression of PSS. Under short-day conditions (10 h:14 h), the fish gained more weight than under long-day conditions (14 h:10 h). A long nighttime induced melatonin secretion and increased the expression of GH mRNA, promoting weight gain in this species. Therefore, we thought that the long day condition in raising olive flounder may be effective in inducing body growth.

Effects of Placing Micro-Implants of Melatonin in Striatum on Oxidiative Stress and Neuronal Damage Mediated by N-Methyl-D-Aspartate (NMDA) and Non-NMDA Receptors

  • Kim, Hwa-Jung;Kwon, Jin-Suk
    • Archives of Pharmacal Research
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    • v.22 no.1
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    • pp.35-43
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    • 1999
  • Overstimulation of both kainate (KA) and N-methyl-D-aspartate (NMDA) receptors has been reported to induce excitatoxicity which can be characterized by neuronal damage and formation of reactive oxygen free radicals. Neuroprotective effect of melatonin against KA-induced excitotoxicity have been documented in vitro and in vivo. It is, however, not clear whether melationin is also neuroportective against excitotoxicity mediated by NMDA receptors. In the present work, we tested the in vivo protective effects of striatally infused melatonin against the oxidative stress and neuronal damage induced by the injection of KA and NMDA receptors into the rat striatum. Melatonin implants consisting of 22-gauge stainless-steel cannule with melatonin fused inside the tip were placed bilaterally in the rat brain one week prior to intrastriatal injection of glutamate receptor subtype agonists. Melatonin showed protective effects against the elevation of lipid peroxidation induced by either KA or NMDA and recovered Cu, Zn-superoxide dismutase activities reduced by both KA and NMDA into the control level. Melatonin also clearly blocked both KA- and NMDA-receptor mediated neuronal damage assessed by the determination of choline acetyltransferase activity in striatal monogenages and by microscopic observation of rat brain section stained with cresyl violet. The protective effects of melatonin are comparable to those of DNQX and MK801 which are the KA- and NMDA-receptor antagonist, respectively. It is suggested that melatonin could protect against striatal oxidative damages mediated by glutamate receptors, both non-NMDA and NMDA receptors.

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Construction of tat-and nef-defective HIV-1 and screening of natural extracts with anti-HIV-1 activity

  • Lee, Ann-Hwee;Song, Man-Ki;Suh, Young-Ah;Sung, Young-Chul
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.77-77
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    • 1995
  • Human immunodeficiency virus type 1 (HIV-1) contains several nonstructural genes which are required for the viral replication and disease pathogenesis. Among them, tat and nef genes encode an essential transactivator of HIV-1 LTR and a pluripotent protein which seems to be essential for the in vivo but not in vitro viral replication, respectively. We constructed two tat and n of defective HIV-1 and tested for their ability to replicate in several T cells. The defective viruses did not replicate in CD4$\^$+/ T cells, but rescued in the recombinant Jurkat-tat cell which also contains tat gene. The replication of tat and nef defective HIV-1 which expresses chloramphenicol acetyltransferase(CAT) gene was easily detected by a sensitive CAT assay. No revertant was identified during the passages of the mutant viruses for more than two months in Jurkat-tat cells. tat and n of defective HIV-1 could be used instead of wild type viruse for several purposes such as inhibitor screening and development of attenuated AIDS vaccine.

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