Ameliorative effect of psoralen on acute liver injury induced by carbon tetrachloride in mice / 中国药科大学学报

@#To investigate the ameliorative effect of psoralen (PSO) on carbon tetrachloride (CCl4)-induced acute liver injury in mice and its potential mechanism, female C57BL/6J mice aged 6-8 weeks were continuously administrated with psoralen or positive control drug diallyl sulfide (DAS) intragastrically for 4 days.On day 4, except that the control group were treated with vehicle control, other groups were all given carbon tetrachloride intraperitoneally to establish a carbon tetrachloride acute liver injury model.Serum biochemical indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected; liver pathological changes were observed by HE staining; cytochrome P450 2E1 (CYP2E1) protein levels were detected by Western blot; the protein level of CYP2E1 were detected by immunohistochemistry (IHC) staining; and the gene levels of CYP2E1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by RT-PCR.Compared with the model group, psoralen could improve the inflammatory cell infiltration and hepatocyte necrosis caused by carbon tetrachloride, significantly reducing the serum ALT and AST levels, down-regulating the inflammatory factors TNF-α and IL-6 levels, and inhibiting CYP2E1 protein expression.The results show that psoralen can ameliorate the acute liver injury induced by carbon tetrachloride in mice, with the possible mechanism inhibiting the protein expression of CYP2E1.

Regulation of il-1 and TNF-α on metabolic enzyme cyp2e1 in immunological liver injury in rats / 中国药理学通报

Aim To investigate the regulation and mechanism of inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) on the drug metabolism enzyme cytochrome P450 2E1 (CYP2E1) during immune-mediated liver injury. Methods By injection of Bacillus Calmette-Guerin(BCG, 125 mg·kg-1) prepared rat model of immunological liver damage. To detection of CYP2E1 probe drug chlorzoxazone in blood concentration changes of rats over time reflects its metabolic activity by high-performance liquid chromatography (HPLC) assay. The changes of IL-1β and TNF-α in liver tissue of rats were detected by ELISA. The expression of CYP2E1 protein was determined by Western blot analysis. Results After 14 days of BCG injection of rats, a large number of mononuclear cells and lymphocytes infiltrated around the liver parenchyma and the portal area, resulting in a large number of granuloma masses with different sizes and diffuse distribution, IL-1β and TNF-α high expression (P < 0.01), CYP2E1 metabolic activity and protein expression were significantly decreased (P < 0.05). The protein content of CYP2E1 was significantly negatively correlated with IL-1β (r=0.222, P=0.027). Activation of PDTC-mediated nuclear factor-kappa B (NF-κB) inhibited the high expression of IL-1β and TNF-α in liver tissue and slowed down the down-regulation of CYP2E1 metabolism and protein expression. Conclusions NF-κB may be involved in the regulation of CYP2E1 by regulating the inflammatory cytokines IL-1β and TNF-α.

Ginsenosides from stems and leaves of ginseng prevent ethanol-induced lipid accumulation in human L02 hepatocytes / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ginsenosides from stems and leaves of ginseng on ethanol-induced lipid deposition in human L02 hepatocytes.</p><p><b>METHODS</b>L02 cells were exposed to ethanol for 36 h and treated with or without ginsenosides. The viability of L02 cells was evaluated by methylthiazolyldiphenyl-tetrazolium bromide assay and the triglyceride (TG) content was detected. Lipid droplets were determined by oil red O staining. Intracellular reactive oxygen species (ROS) production and the mitochondrial membrane potential were tested by flow cytometry. The ATP level was measured by reverse phase high performance liquid chromatography. The expression of cytochrome p450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) was detected by reverse transcriptase-polymerase chain reaction and Western blotting, respectively.</p><p><b>RESULTS</b>Ethanol exposure resulted in the increase of TG level, lipid accumulation and ROS generation, and the decrease of mitochondrial membrane potential and ATP production in the cells. However, ginsenosides significantly reduced TG content (9.69±0.22 μg/mg protein vs. 4.93±0.49 μg/mg protein, P<0.01), and ROS formation (7254.8±385.7 vs. 5825.2±375.9, P<0.01). Meanwhile, improvements in mitochondrial membrane potential (10655.33±331.34 vs. 11129.52±262.35, P<0.05) and ATP level (1.20±0.18 nmol/mg protein vs. 2.53±0.25 nmol/mg protein, P<0.01) were observed by treatment with ginsenosides. Furthermore, ginsenosides could down-regulate CYP2E1 expression (P<0.01) and upregulate PPARα expression (P<0.01) in ethanol-treated cells.</p><p><b>CONCLUSIONS</b>Ginsenosides could prevent ethanol-induced hepatocyte steatosis in vitro related to the inhibition of oxidative stress and the improvement of mitochondrial function. In addition, the modulation of CYP2E1 and PPARα expression may also play an important role in the protective effect of ginsenosides against lipid accumulation.</p>

A Fruit Extract of Paeonia anomala Attenuates Chronic Alcohol-induced Liver Damage in Rats

Prolonged alcohol consumption causes alcoholic liver damage due to the generation of reactive oxygen species, the accumulation of fatty acids, and an increase in inflammatory cytokines in the liver. In this study, the protective effect of a fruit extract of Paeonia anomala (FEPA) against chronic alcohol-induced liver damage was evaluated in Sprague-Dawley rats fed an ethanol or a control Lieber-DeCarli diet for 5 weeks to induce alcoholic liver damage. FEPA (50, 25, and 10 mg/kg body weight/day) as well as the reference control silymarin (25 mg/kg body weight/day) were administered along with the ethanol diet. FEPA protected against increases in alanine aminotransferase and aspartate aminotransferase in serum and attenuated alcohol-induced increases in triglycerides, tumor necrosis factor alpha, thiobarbituric acid-reactive substances, and cytochrome P450 2E1 enzyme activity in the liver compared with the group treated with ethanol only. Anti-oxidative defenses such as the total glutathione level and glutathione peroxidase activity were increased by FEPA treatment. These results suggest that FEPA exerts protective effects against chronic alcohol-induced liver damage by attenuating hepatosteatosis and pro-inflammatory cytokine production and enhancing anti-oxidative defense mechanisms in the liver.

Involvement of brain CYP2 E1 in damage to neuronal cells induced by lipopolysaccharide / 中国药理学通报

Aim To investigate the interactions be-tween the neuroinflammation caused by lipopolysaccha-ride(LPS) and brain CYP2E1.Methods The human cholinergic neuroblastoma cell line IMR-32 was treated with LPS ( 0.1 mg · L-1 , 1.0 mg · L-1 ) , and the LDH and SOD activities were determined after 24 h in-cubation .In order to determine the roles of MAPK sig-naling pathway in the regulation of CYP 2E1 by LPS, the IMR-32 cells were treated with p38 pathway inhibi-tor SB203580 or ERK pathway inhibitor U 0126 for 45 min before the incubation with LPS .The human do-paminergic neuroblastoma cell line SH-SY5Y with CYP2 E1 over-expression was established . The LDH and SOD activities were determined in SH-SY5 Y cells over-expressed CYP2 E1 and control cells treated with LPS(0.1 mg· L-1 , 1.0 mg· L-1 ) for 24 h.Results The levels of LDH in IMR-32 cells treated with high-dose LPS were increased by 1.38-fold ( P <0.01 ) compared with the control group , and the levels of SOD reduced by 15.0%( P <0.01 ) .Compared with the control, CYP2E1 mRNA and protein levels in IMR-32 cells treated with high-dose LPS were increased by 1.25-fold(P<0.01) and 1.19-fold(P<0.05).The up-regulation of CYP2E1 by LPS could be attenuated by SB203580 and U0126 pretreatment.Compared with the control cells, the CYP2E1 over-expression in-creased LDH levels by 1.28-fold ( P<0.01 ) and de-creased SOD levels by 3.53-fold ( P<0.01 ) after the low-dose of LPS treatment .The CYP2E1 over-expres-sion increased LDH levels by 1.54-fold ( P <0.01 ) and decreased SOD levels by 2.17-fold( P<0.01) af-ter the high-dose of LPS treatment , compared with the control cells.Conclusions LPS can induce CYP2E1 mRNA and protein levels , and the p38 and ERK sig-naling pathway may be involved in the regulation .The elevated CYP2 E1 levels aggravate the damage to neuro-nal cells caused by LPS .Brain CYP2E1 may be an im-portant contributing factor to the pathological process of neuroinflammatory injury .

Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population / Caracterización de polimorfismos de los genes ADH2, ADH3, ALDH2 y CYP2E1 y su relación con el alcoholismo en una población colombiana

Objective: Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism. Methods: ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells. Results: Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant. Conclusions: This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2*2, CYP2E1*1 combined with genotype homozygous ALDH2*1 found in this study could be leading to the population to a potential risk to alcoholism.

Objetivo: Identificar y caracterizar los polimorfismos de los genes ADH2, ADH3, ALDH2 y CYP2E1 de colombianos residentes en la ciudad de Bogotá y determinar su posible relación con el alcoholismo. Métodos: Se determinaron los genotipos ADH2, ADH3, ALDH2 y CYP2E1 a una población de 148 individuos con un consumo no problemático de alcohol y 65 individuos con alcoholismo. La genotipificación se realizó con sondas TaqMan y PCR-RFLP, el ADN se obtuvo de células blancas de sangre periférica. Resultados: Se encontró diferencia significativa en la historia familiar de alcoholismo y el uso de otras sustancias psicoactivas. Cuando se consideraron frecuencias alélicas para cada categoría (género), la frecuencia de portadores del alelo A2 en ADH2 se encontró mayor en los pacientes masculinos que los controles. En las mujeres, la frecuencia relativa para el alelo C1 de CYP2E1 fue menor en controles que en alcohólicos. El locus ALDH2 es monomórfico. No se observaron diferencias significativas en las distribuciones alélicas de los loci examinadas al comparar las dos poblaciones, sin embargo al estratificar las mismas se encontró una tendencia a que esas diferencias fueran significativas. Conclusiones: Este estudio nos permite concluir la asociación positiva entre historia familiar de alcoholismo y el alcoholismo, lo que sugiere que existe una predisposición hereditaria favorable. Dado que la dependencia de sustancias requiere la interacción de múltiples genes como ADH2*2, CYP2E1*1 combinado con el genotipo homocigótico ALDH2*1 hallados en este estudio podría estar llevando a la población a un riesgo potencial hacia el alcoholismo.

Protective effect of Compound Ginkgo against acute alcohol-induced liver injury and its mechanism / 中国药理学与毒理学杂志

OBJECTIVE ToobservetheprotectiveeffectandmechanismofCompoundGinkgo biloba(CGB)againstalcohol-inducedliverinjury.METHODS MiceweregivenCGB0.125,0.25and 0.75 g·kg -1 ,Ginkgo biloba extract (GBE)0.1 25 g·kg -1 and bifendate(Bif)0.1 5 g·kg -1 for 8 weeks, respectively.At the end of 4th week the mice were given wine by gavage (56% V/V,0.01 L·kg -1 ), and (56% V/V,0.016 L·kg -1 )at the end of the 8th week.The serum was obtained to measure alanine transaminase (GPT),aspartate aminotransaminase (GOT),mitochondrial aspartate aminotransferase (mGOT)and tumor necrosis factor-α(TNF-α).Liver histopathology was revealed by HE staining.The protein expression of cytochrome P450 (CYP)2E1 ,NF-E2-related factor 2 (Nrf2)and TNF-αin the liverwasanalyzedbyWesternblotting.RESULTS Comparedwithnormalcontrolgroup,theactivitiesof GOT and mGOT were increased in model group (P0.05).Fatty degeneration and neutrophil infiltration were significantly ameliora-ted in CGB 0.25 and 0.75 g·kg -1 groups.Preliminary mechanism research showed CGB not only increased the protein expression of Nrf2 with a positive dose-effect relationship (r=0.942,P<0.01 ), but reduced the protein expression of hepatic CYP2 E1 and the level of TNF-αin hepatic tissue with a negative dose-effect relationship (r=-0.987,P<0.05;r=-0.940,P<0.05).In addition.The level ofTNF-αwasalsosignificantlydecreasedintheserum(P<0.05,P<0.01).CONCLUSION CGB may protect the liver fro m acute alcoholic injury and the mechanis m may be that it increases the protein expression of Nrf2,restrains the protein expression of hepatic CYP2E1 and TNF-αand reduces the TNF-αlevel in the serum.

Anti-oxidant activities of kiwi fruit extract on carbon tetrachloride-induced liver injury in mice / 대한수의학회지

The kiwi (Actinidia deliciosa) is well known to contain anti-oxidants. In this study, we investigated the anti-oxidant effects of kiwi extract on carbon tetrachloride (CCl4) induced liver injury in BALB/c mice. The radical scavenging effect of 80% methanol extract of Halla-Gold kiwi was observed. For the animal study, mice were randomly divided into four groups: normal group, CCl4-induced model group, kiwi extract administered group, and silymarin treated group. The kiwi extract was provided daily for 10 days. At the 24 h after last administration, CCl4 was injected. The kiwi extract showed strong inhibitory effect of DPPH radicals and superoxide scavenging. In animal study, administration of CCl4 resulted in significantly elevated plasma levels of ALT and AST but they decreased in kiwi-extract pretreated group. Anti-oxidant enzymes such as GSH-px and GSH-rd were restored in the kiwi extract treatment group. Histopathological degeneration was also prevented in the kiwi extract treated group compared with of the control group, which exhibited CCl4-induced hepatotoxicity. On the basis of the obtained results, it can be concluded that kiwi extract showed protective effects, not only as anti-oxidant effects, but also in the protection of hepatotoxicity in CCl4-intoxicated mice.

Clinical Outcomes of Occupational Exposure to N,N-Dimethylformamide: Perspectives from Experimental Toxicology

N,N-Dimethylformamide (DMF) is globally used as an organic solvent in the production of synthetic leather and resins because of its low volatility, making it an attractive industrial material. Despite its excellent property as a chemical solvent, utilization of DMF is somewhat controversial nowadays due to its hazardous effects on exposed workers in work places. Many toxification cases are being reported globally and the number of cases of liver damage is still increasing in developing countries. On account of this, a series of epidemiologic surveys are being conducted to understand the degrees of liver damage caused by DMF exposure. Furthermore, many investigations have been performed to clarify the mechanism of DMF-induced liver toxicity using both human and experimental animal models. This review summarizes the current occupational cases reported on liver damage from workers exposed to DMF in industrial work places and the research results that account for DMF-induced liver failure and possible carcinogenesis. The findings reviewed here show the synergistic toxicity of DMF exposure with other toxicants, which might occur through complicated but distinct mechanisms, which may extend our knowledge for establishing risk assessments of DMF exposure in industrial work places.

Identification of Polymorphisms in CYP2E1 Gene and Association Analysis among Chronic HBV Patients

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257 , considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

Effect of Tiopronin on Cytochrome P_(450)2E1 Expression in Liver of Rats with Alcoholic Fatty Liver / 中国药房

OBJECTIVE:To explore the effect of tiopronin on the expression of cytochrome P4502E1(CYP2E1)in liver of rats with alcoholic fatty liver.METHODS:30 Wistar rats were randomly divided into 3 groups:group A(blank control group),group B(model group)and group C(tiopronin group).Group B and group C were given 50% alcohol intragastrically to establish alcoholic fatty liver model,while group C were intervened with tiopronin(0.15 g?kg-1?d-1 administered at 1 hour after alcohol administration)for 5 consecutive weeks.Then all the rats were sacrificed with AST and ALT levels in serum determined.The CYP2E1 expression was detected by RT-PCR;and the pathologic changes of the liver tissues were observed.RESULTS:In group B compared with group A,serum levels of AST,ALT and CYP2E1 expression were significantly higher(P

Roles of hepatocyte cytochrome P450 2E1 in nonalcoholic steatosis of rat liver / 第三军医大学学报

Objective To study the roles of hepatocyte cytochrome P450 2E1 in model of nonalcoholic steatosis in rats Methods A total of 40 Wistar rats were randomly divided into two groups: control group (C) and high fat diet induced fatty liver group (H) The expression of hepatocyte cytochrome P450 2E1 antigen in rat model of nonalcoholic steatosis was detected by immunohistochemical method and Western blotting Malondialdehyde (MDA) contents were also determined Results MDA contents and the expression of hepatocyte cytochrome P450 2E1 antigen in rat model of nonalcoholic steatosis induced by high fat diet were higher than those in the normal controls ( P

The Effects of Diethyldithiocarbamate on the Metabolism and Hepatotoxicity of Trichloroethylene / 대한산업의학회지

OBJECTIVES: The purpose of this study was to evaluate the trichloroethylene (TCE) metabolism, acute toxicity, and the effects of diethyldithiocarbamate (DDTC) on the acute toxicity in TCE-intoxicated rats. METHODS: TCE was administered orally at doses of 600, 1,200 and 2,400 mg/kg of body weight following pretreatment with either saline or 500 mg/kg of DDTC. 12 hours after administration of TCE, the concentrations of TCE, trichloroacetic acid (TCA) and trichloroethanol (TCEOH) in the blood and solid organs, and the histopathological changes in each organ were examined. RESULTS: The level of CYP2E1 markedly decreased in the DDTC-pretreated groups. The CYP2E1 content in the TCE-treated rats increased in a dose-dependent manner. The concentrations of TCE and TCEOH were highest in the liver, and the level of TCA was highest in the blood. The DDTC-pretreated rats had a markedly increased level of TCE and decreased levels of TCA and TCEOH, than the rats pretreated with saline. These findings indicated that CYP2E1 was important in the metabolism of TCE. From the histopathological findings, centrilobular necrosis was observed in the livers of the TCE-treated rats, but no significant change was found in those rats pretreated with DDTC. CONCLUSIONS: DDTC is considered to be effective in protecting TCE-induced hepatic damage because it inhibits the TCE metabolism.

Interaction between Genetic Polymorphisms of CYP2E1 & NAT1 and Smoking in Lung Cancer Development (Preliminary report) / 대한암학회지

PURPOSE: The interactive effects of genetic polymorphisms of cytochrome P4502E1 (CYP2E1) & N-acetyltransferase 1 (NAT1) and smoking on lung cancer development were evaluated in hospital based case-control study. MATERIALS AND METHODS: Male lung cancer patients (N= 157) and the male patients with no present or previous history of systemic illnesses who visited the urology department (N=138) were recruited (1998-1999). CYP2E1 & NAT1 genotypes were determined by PCR-RFLP method using RsaI and MboII digestion, respectively. RESULTS: CYP2E1 c2 or NAT1 *10 allele did not increased the risk of lung cancer. Heavy smokers (35

Relationship between genetic polymorphisms of cytochrome P450 2E1 and gastric cancer / 中华消化杂志

Objective To study the relationship between genetic polymorphisms of cytochrome P450 2E1(CYP2E1) and susceptibility to gastric cancer. Methods Genotype of CYP2E1 was determined by polymorphism (PCR-RFLP) analysis on DNA in 92 patients with gastric cancer and 92 controls in case-control study. Results The results showed that the frequency of the wild-type genotype (C1/C1) detected by RsaⅠ digestion was 66.3% and 48.9% in gastric cancer group and controls, respectively (P

Effects of Genetic Factor, Life Styles, and Diet on Urinary Hippuric Acid Excretion in Toluene Exposed Workers / 대한산업의학회지

OBJECTIVES: The purpose was to investigate the distributions and the effects of genetic polymorphism of aldehyde dehydrogenase 2(ALDH2), cytochrome P450 1A1(CYP1A1), and cytochrome P450 2E1(CYP2E1) on the toluene metabolism. METHODS: The subjects consisted of 160 workers who were exposed to toluene in different industries such as paint manufacturing, painting on steel and wood products, printing, bonding, and coating. The exposed toluene level was monitored by passive air sampler, and the questionnaire variables were age, sex, smoking, drinking, previous nights drinking, use of personal protective equipment, work duration, and taking benzoic acid containing food. The urinary hippurric acid collected in the end of shift was corrected by urinary creatinine concentration. The genotypes of ALDH2, CYP1A1, and CYP2E1 were investigated using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) methods with DNA extracted from venous blood. RESULTS: The geometric mean and the geometric standard deviation of urinary hippuric acid concentration were 0. 44 g/g creatinine and 2. 80. The urinary hippuric acid concentration was significantly related to personal exposed toluene level among personal exposed toluene level, use of personal protective equipment, and benzoic acid containing food diet. The slope differences of the regression for ALDH2, CYP1A1, and CYP2El genetic polymorphism, age, smoking, and work duration tended to be significant. In multiple regression analysis, the regression coefficient of toluene, ALDH2, CYP1A1, CYP2E1 genetic polymorphism were significant. CONCLUSIONS: Prom the above results, urinary hippuric acid level after toluene exposure was significantly affected by the genetic polymorphism of ALDH2, CYP1A1, CYP2E1. It is needed further investigation of the urinary hippuric acid level considering the effect of genetic polymorphism.

Cytochrome P450 2E1 Polymorphisms and Genetic Susceptibility to Cervical Cancer / 대한암학회지

PURPOSE: Interindividual genetic differences in susceptibility to chemical carcinogens are one of the most important host factors in human cancer. The genetically determined differences in metabolism, related to cytochrome P450 (CYP450) genes have been reported to be associated with various cancer susceptibility. The present study was set up to establish the frequency of the polymorphic genotypes of two CYP450 (CYP2E1/PstI and CYP2E1/DraI) isozymes in Korea, to evaluate a possible increased incidence of the genotype associated with higher cervical cancer risks among Korean cervical cancer patients. MATERIALS AND METHODS: In this study, extracted DNAs from 228 cervical cancer patients and 360 normal healthy controls were analysed with the polymerase chain reaction-restriction fragment length polymosphism (PCR-RFLP) method. RESULTS: In the CYP 2E1 genotypes, detected by PstI or RsaI digestion, there were no statistically remarkable differences between the cervical cancer patients and control groups. And when the cervical cancer patients were divided into subgroups with respect to the age, the frequency of CYP 2E1/PstI polymorphisms in the cervical cancer patients under the 40 years old was not significantly higher compared to the controls or the patients above the 40 years old and, c1/c1 genotype was prominent in this type of polymorphism. The frequency of CYP 2E1/DraI polymorphisms in the cervical cancer patients was not significantly higher compared to the controls, and D/D genotype was prominent in this type of polymorphism. In cervical carcinoma, the polymorphic genotypes of CYP 2E1 were not correlated to other parameters including clinical stage, histological tumor type, and degree of differentiation. CONCLUSION: These results suggest that individuals carrying CYP 2E1/PstI (c1/c1) or CYP 2E1/DraI (D/D) alleles are not genetically susceptible to cervical cancer in Korea.

Establishment of model with exogenous human CYP2E1 expression and inducement of substrates / 中国病理生理杂志

AIM: To investigate the effect of ethanol and chemical carcinogen N,N'-dinitrosopiperazine(DNP) on the exogenous expression of CYP2E1.METHODS: Exogenous hCYP2E1 was introduced into NIH3T3 mediated by lipofectamine. Then the integration of exogenous gene was showed by Southemrn blot. After treated with different concentration of ethanol and DNP,RT-PCR and Western blotting were used to analyze the expression change of hCYP2E1 in NIH 3T3. RESULTS: Two cell clones with integration and stable expression of exogenous hCYP2E1 were obtained. The RT-PCR and Western blotting showed that human CYP2E1 mRNA and protein expression was enhanced with increase in ethanol and DNP concentration. CONCLUSION: Exogenous expression of hCYP2E1 was steadily induced by ethanol and DNP. The mechanism may be due to the activation of its transcription. The DNP carcinogenesis might be related to its in situ activation by CYP2E1.