• 제목/요약/키워드: xenobiotic metabolism

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콜타르가 함유된 페인트 사용 조선업 근로자에서 요중 1-hydroxypyrene glucuronide와 대사효소 유전자 다형성에 관한 연구 (Urinary 1-hydroxypyrene glucuronide and genetic polymorphisms of xenobiotic metabolism enzymes in shipbuilding workers using coal tar paint)

  • 이경호;이정미;최인미;김재용;임형준;이상윤;윤기정;고상백;최홍렬
    • 한국환경성돌연변이발암원학회지
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    • 제20권1호
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    • pp.34-39
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    • 2000
  • Although shipbuilding workers were exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs), limited number of studies were conducted to evaluate the biomarkers related to PAH exposure in painting workers in shipbuilding industry. One hundred and thirty three workers including 73 employees using coal tar paints were recruited from a shipbuilding company located in South Korea. Urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Glutathione S-transferase (GST)M1 and GSTT1 genotypes were assessed by multiplex PCR. Information on demographic characteristics, smoking gabit, diet, job title, use of personal protective equipments were collected by self-administered questionnaire. Urinary 1-OHPG were higher in workers using coal tar paints than in workers using general paints, however, the difference was not statistically significant (p=0.20, Mann-Whitney U test). Urinary 1-OHPG levels in smokers were higher than in non-smokers (p<0.05 by Mann-Whitney U test) and there was a significant increase in urinary 1-OHPG levels with the numbers of cigarettes consumed per day (Spearman's correlation coefficient = 0.28, p=0.02). Genetic polymorphisms of GSTM1 and GSTT1 did not influence the level of 1-OHPG in study subjects. Multiple regression analysis show that smoking is the only significant predictor for lon-transformed 1-OHPG (overall model R2=0.1). These results suggest that workers using coal tar paints were exposed to significant amount of PAHs and individual difference in xenobiotic metabolism might affect the levels of internal dose of PAHs.

The Alcohol-inducible form of Cytochrome P450 (CYP 2E1): Role In Toxicology and Regulation of Expression

  • Novak, Raymond F.;Woodcroft, Kimberley J.
    • Archives of Pharmacal Research
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    • 제23권4호
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    • pp.267-282
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    • 2000
  • Cytochrome P45O (CYP) 2E1 catalyzes the metabolism of a wide variety of therapeutic agents, procarcinogens, and low molecular weight solvents. CYP2E1-catalyzed metabolism may cause toxicity or DNA damage through the production of toxic metabolites, oxygen radicals, and lipid peroxidation. CYP2E1 also plays a role in the metabolism of endogenous compounds including fatty acids and ketone bodies. The regulation of CYP2E1 expression is complex, and involves transcriptional, post-transcriptional, translational, and post-translational mechanisms. CYP2E1 is transcriptionally activated in the first few hours after birth. Xenobiotic inducers elevate CYP2E1 protein levels through both increased translational efficiency and stabilization of the protein from degradation, which appears to occur primarily through ubiquitination and proteasomal degradation. CYP2E1 mRNA and protein levels are altered in response to pathophysiologic conditions by hormones including insulin, glucagon, growth hormone, and leptin, and growth factors including epidermal growth factor and hepatocyte growth factor, providing evidence that CYP2E1 expression is under tight homeostatic control.

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소각장 근로자에서 환경성 발암물질 대사효소의 유전다형성이 PAH-DNA adduct와 뇨중 PAM 대사산물의 관계에 미치는 영향 (Association of PAH-DNA adducts and urinary PAM metabolites influenced by genetic polymorphisms of xenobiotic metabolism enzymes in incinerating workers)

  • 이정미;;이경호;하미나;최성우;이상윤;임형준;최재욱;황응수;조수헌;강대희
    • 대한예방의학회:학술대회논문집
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    • 대한예방의학회 1999년도 제51차 추계 학술대회 연제집
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    • pp.94-95
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    • 1999
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Effect of Ethanol extract isolated from Peacilomyces tenuipes against oxidative stress in Hepa1c1c7 cell

  • Kim, Deok-Song;Seo, Eun-Sun;Lee, Kyung-Jin;Lee, Jong-Bin
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2003년도 춘계학술대회 논문집
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    • pp.76-76
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    • 2003
  • Oxidative stress is considered to be associated with many diseases, such as inflammatory and cardiovascular diseases, aging, and cancer. An important etiological mechanism of these diseases may be a causal relationship between the presence of oxidants and the generation of lipid hydroperoxides derived from enzymatic reactions or xenobiotic metabolism. (omitted)

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PULMONARY XENOBIOTIC CONJUGATION IN THE ISOLATED PURFUSED RABBIT LUNG AND IN VITRO: EFFECT OF ETHANOL

  • Yang, C.Mierha;Carlson, Gary P.
    • Toxicological Research
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    • 제7권2호
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    • pp.191-208
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    • 1991
  • Pulmonary conjugation pathways may be important for the metabolism of xenobiotics introduced via airways of systemically. The objective of this study was to determine the pulmonary conjugating capacity in both the isolated perfused rabbit lung (IPRL) and in vitro, and the ability of ethanol to alter the above. The IPRL was capable of conjugating glutathione (GSH) with either 1-chloro-2,4-dinitrobenzene (CDNB) of 1,2-epoxy-(p-nitrophenoxy) propane(ENP). The pulmonary GSH conjugation with ENP was inhibited by cibacron blue, indicating the presence of glutathione-S-transferase (GST) u and/or classes, but it was not altered by buthionine sulfoximine, a selective inhibitor of Gamma-glutamylcysteine synthetase.

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Characterization of Copper/Zinc-Superoxide Dismutase (Cu/Zn-SOD) Gene from an Endangered Freshwater Fish Species Hemibarbus mylodon (Teleostei; Cypriniformes)

  • Lee, Sang-Yoon;Kim, Keun-Yong;Bang, In-Chul;Nam, Yoon-Kwon
    • Fisheries and Aquatic Sciences
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    • 제14권1호
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    • pp.43-54
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    • 2011
  • Gene structure of copper/zinc-superoxide dismutase (Cu/Zn-SOD; sod1) was characterized in Hemibarbus mylodon (Teleostei; Cypriniformes), an endangered freshwater fish species in Korean peninsula. Full-length cDNA of H. mylodon SOD1 consisted of a 796-bp open reading frame sequence encoding 154 amino acids, and the deduced polypeptide sequence shared high sequence homology with other orthologs, particularly with regard to metal-coordinating ligands. Genomic structure of the H. mylodon sod1 gene (hmsod1; 1,911 bp from the ATG start codon to the stop codon) was typical quinquepartite (i.e., five exons interrupted by four introns); the lengths of the exons were similar among species belonging to various taxonomic positions. The molecular phylogeny inferred from sod1 genes in the teleost lineage was in accordance with the conventional taxonomic assumptions. 5'-flanking upstream region of hmsod1, obtained using the genome walking method, contained typical TATA and CAAT boxes. It also showed various transcription factor binding motifs that may be potentially involved in stress/immune response (e.g., sites for activating proteins or nuclear factor kappa B) or metabolism of xenobiotic compounds (e.g., xenobiotic response element; XRE). The hmsod1 transcripts were ubiquitously detected among tissues, with the liver and spleen showing the highest and lowest expression, respectively. An experimental challenge with Edwardsiella tarda revealed significant upregulation of the hmsod1 in kidney (4.3-fold) and spleen (3.1-fold), based on a real-time RT-PCR assay. Information on the molecular characteristics of this key antioxidant enzyme gene could be a useful basis for a biomarker-based assay to understand cellular stresses in this endangered fish species.

산업폐기물 소각장 근로자에서 요중 PAHs 대사산물과 혈중 aromatic-DNA adducts (Association of PAH-DNA adducts and Urinary PAH metabolites influenced by polymorphisms of xenobiotic metabolism enzymes in industrial wase incinerating workers)

  • 이경호;;최인미;최재욱;조수헌;강대희
    • 한국환경성돌연변이발암원학회지
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    • 제22권4호
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    • pp.303-311
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    • 2002
  • This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

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Constitutive Androstane Receptor (CAR)의 활성, 에너지 대사 및 세포의 증식과 사멸의 조절에 대한 CAR의 cross-talk 기전 (The Cross-talk Mechanisms of Constitutive Androstane Receptor (CAR) in the Regulation of its Activity, Energy Metabolism, Cellular Proliferation and Apoptosis)

  • 민계식
    • 생명과학회지
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    • 제30권2호
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    • pp.211-220
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    • 2020
  • CAR의 활성은 리간드 결합 뿐만 아니라, 세포외신호전달 경로를 통한 관련 조절인자들의 인산화, 전사 조절인자들과의 상호작용, 그리고 coactivators 및 corepressors의 동원, 분해 및 발현 등에 의해 조절되며, 이러한 CAR의 활성 조절은 또한 외인성 화학물질과 에너지 대사, 세포의 증식 및 사멸을 포함한 다양한 생리적 항상성 조절에 영향을 미친다. CAR는 ERK1/2의 신호전달경로에 의해 인산화되어 Hsp-90/CCRP와 복합체를 형성하여 세포질 내에 잔류하는 반면, PB는 ERK1/2를 억제하여 downstream 신호전달 조절인자들의 탈인산화를 유발하고, 활성화된 RACK-1/PP2A를 동원하여 CAR를 탈인산화 함으로써 핵 이동 및 전사 활성을 유도한다. CAR의 활성은 FoxO1 및 PGC-1α와의 cross-talk을 통하여 각각 전사 활성 억제와 ubiquitination을 통한 단백질 분해를 유도하여 당합성과정에 관여하는 PEPCK 및 G6Pase 유전자의 발현을 억제한다. CAR에 의한 지방의 합성과 산화 조절은 각각 PPARγ 및 PPARα와의 cross-talk에 의한 PGC-1α의 분해와 CPT-1의 발현 억제 또는 PGC-1α와의 결합을 통해 지방 합성 유전자의 발현 억제와 조직 특이적 산화 억제 또는 촉진으로 이루어진다. CAR는 FoxO1의 억제를 통한 p21의 발현 억제와 cyclin D1의 발현을 유도하여 세포 증식을 촉진하는 반면, GADD45B의 발현을 통한 MKK7과 JNK1의 활성을 억제하여 세포 사멸을 억제한다. 결론적으로, CAR는 세포외신호전달 경로와 세포내 조절인자들과의 다양한 상호작용을 통하여 외인성 화학물질의 대사뿐만 아니라 에너지 대사 및 세포의 성장과 사멸의 조절을 통한 항상성 유지에 관여한다.

Bacterial community structure of paddy fields as influenced by heavy metal contamination

  • Tipayno, Sherlyn;Samaddar, Sandipan;Chatterjee, Poulami;Halim, MD Abdul;Sa, Tongmin
    • 한국작물학회:학술대회논문집
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    • 한국작물학회 2017년도 9th Asian Crop Science Association conference
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    • pp.245-245
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    • 2017
  • Heavy metal pollution of agricultural soils affects land productivity and has impact on the quality of surrounding ecosystem. Soil microbial community parameters are used as reliable indices for assessing quality of agricultural lands under metal stress. This study investigated bacterial community structure of polluted and undisturbed paddy soils to elucidate soil factors that are related to alteration of bacterial communities under conditions of metal pollution. No obvious differences in the richness or diversity of bacterial communities were observed between samples from polluted and control areas. The bacterial communities of three locations were distinct from one another, and each location possessed distinctive set of bacterial phylotypes. The abundances of several phyla and genera differed significantly between study locations. Variation of bacterial community was mostly related to soil general properties at phylum level while at finer taxonomic levels concentrations of arsenic and lead were significant factors. According to results of bacterial community functional prediction, the soil bacterial communities of metal polluted locations were characterized by more abundant DNA replication and repair, translation, transcription and nucleotide metabolism pathway enzymes while amino acid and lipid metabolism as well as xenobiotic biodegradation potential was reduced.Our results suggest that the soil microbial communities had adapted to the elevated metal concentrations in the polluted soils as evidenced by changes in relative abundances of particular groups of microorganisms at different taxonomic resolution levels, and by altered functional potential of the microbial communities.

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Trichloroethylene 처리한 흰쥐의 간 미크로좀 Alcohol dehydrogenase와 Aldehyde dehydrogenase 활성도에 관한 연구 (Studies on Hepatic Microsomal Alcohol Dehydrogenase(ADH) and Aldehyde Dehydrogenase(ALDH) Activities in Rats Treated with Trichloroethylene)

  • 김기웅;강선규;양정선;박인정;문영한
    • 한국산업보건학회지
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    • 제4권2호
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    • pp.148-156
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    • 1994
  • Chloral hydrate(CH), an intermediate metabolite of trichloroethylene(TRI) is reduced to trichloroethanol(TCE-OH), and is oxidized to trichloroacetic acid(TCA) by the nicotinamide adenine dinucleotide(NAD)-dependent enzymes such as alcohol dehydrogenase(ADH) and aldehyde dehydrogenase(ALDH) in liver. This study was performed to find out the change of activity of ADH and ALDH with increasing amount of TRI. Intraperitoneal injection of TRI were done to the male Sprague Dawely rats(mean body weight, $170{\pm}10g$) in com oil at the dosage of 150, 300, 600 mg/kg for 2 days. The results of experiments are following : 1. The contents of xenobiotic metabolic enzymes in liver are tended to be decreased with increasing amount of, but not significantlly (p>0.05). 2. Activity of ADH in microsome is decreased(p<0.05), and activity of ALDH is increased with amount of TRI(P<0.05). 3. Total trichloro-compounds(TTC) concentration in urine are increased with amount of TRI, but the ratio of between the TCE-OH and the TCA were not shown any critical change. These results suggests that the ALDH in microsome may be related to metabolism of TRI, but ADH was nothing less than the effected to metabolism of TRI.

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