CYP1A2 is an important cytochrome P450 enzymes, which is involved in metabolism of many clinical drugs and activation of some precarcinogens. CYP1A2 activity can be influenced by various factors including genetic polymorphism, drugs, food and so on, in which the CYP1A2 genetic polymorphism is the basis of difference on the activity and induction of CYP1A2. Therefore,the genotyping of CYP1A2 plays an important part in individualization of therapy.
Carcinogens ; metabolism ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Genotype ; Humans ; Inactivation, Metabolic ; genetics ; Polymorphism, Genetic ; genetics

OBJECTIVETo investigate the characteristics of microbial degradation of aniline by a stable bacterial consortium.

METHODSThe bacterial consortium was isolated from activated sludge treating chemical wastewater using aniline as the sole source of carbon and nitrogen by enrichment and isolation technique. The biomass was measured as optical density (OD) at 510 nm using a spectrophotometer. Aniline concentrations were determined by spectrophotometer. The intermediates of aniline degradation were identified by GC/MS method.

RESULTSThe bacterial consortium could grow at a range of aniline concentrations between 50 and 500 mg/L. The optimal pH and temperature for aniline degradation were determined to be 7.0 and 30, respectively. The presence of NH4NO3 as an additional nitrogen source (100-500 mg/L) had no adverse effect on bacterial growth and aniline degradation. The presence of heavy metal ions, such as Co2+, Zn2+, Ni2+, Mn2+ and Cu2+ had an inhibitory effect on aniline degradation.

CONCLUSIONSThe isolated bacterial consortium can degrade aniline up to 500 mg/L effectively and tolerate some heavy metal ions that commonly exist in chemical wastewater. It has a potential to be applied in the practical treatment of aniline-containing wastewater.

Aniline Compounds ; metabolism ; Bacteria ; Biomass ; Bioreactors ; Carcinogens ; metabolism ; Chemical Industry ; Hydrogen-Ion Concentration ; Metals, Heavy ; analysis ; Waste Disposal, Fluid ; methods ; Water Pollutants ; metabolism

Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins.
Animals ; Carcinogens/*metabolism/*toxicity ; Cell Cycle/drug effects ; Cell Line ; Cell Proliferation ; Clonorchis sinensis/*metabolism ; Dimethylnitrosamine/*toxicity ; Epithelial Cells/*drug effects ; Humans

Adenocarcinoma ; chemically induced ; metabolism ; Animals ; Apoptosis ; drug effects ; Carcinogens ; toxicity ; Histocompatibility Antigens Class I ; metabolism ; Humans ; Interferon-gamma ; metabolism ; Interleukin-2 ; metabolism ; Lung Neoplasms ; chemically induced ; metabolism ; Lymphocytes ; cytology ; metabolism ; Pulmonary Surfactant-Associated Protein C ; metabolism ; Sterigmatocystin ; toxicity

The 8-hydroxydeoxyguanosine (8-OH-dG), DNA adduct produced by oxygen radical-induced hydroxylation of C-8 position of guanine residue is accepted as to cause mutation and associate with carcinogenesis, and there are many carcinogens those produce oxygen radicals. Although many carcinogens have been accepted to induce bladder tumor, there is little known about the mechanism of carcinogenesis by these carcinogens. Following administration of bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), 4-Aminobiphenyl (4-ABP), 2-naphthylamine (2-NA) and N-methyl-N-nitrosourea (MNU) to human normal bladder epithelial cell, the results were obtained.1. Following administration of aromatic amine carcinogen, BBN, 4-ABP and 2-NA, the content of 8-OH-dG was increased to about 30-35 % although some variation of time existed according to the kinds of carcinogens. 2. Following administration of MNU, the content of 8-OH-dG was increased to about less than 3 % over all times. 3. Following administration of H2O2 that produce oxygen radicals without metabolism, the content of 8-OH-dG was increased to about 37 %. From this result, it can be supposed that the in crease of 8-OH-dG by carcinogens is induced by oxygen radical.The results obtained suggest that there are some enzymes in bladder epithelium that are related to metabolism of aromatic amine carcinogens and modification of DNA in bladder epithelial cell by the oxygen radicals, that is Formation of 8-OH-dG, is induced in carcinogenesis of bladder tumor byaromatic amine carcinogens.
2-Naphthylamine ; Carcinogenesis ; Carcinogens* ; DNA* ; Epithelial Cells ; Epithelium ; Guanine ; Humans* ; Hydroxylation ; Metabolism ; Methylnitrosourea ; Oxygen ; Reactive Oxygen Species ; Urinary Bladder Neoplasms ; Urinary Bladder*

Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycolytic pathway. Surrounding macrophages and newly formed granulation tisssue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application of FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue.
Adenosine Triphosphate ; Anoxia ; Biological Factors ; Blood Volume ; Carcinogens ; Cell Membrane ; Glucose* ; Glycolysis ; Hexokinase ; Humans ; Macrophages ; Membranes ; Metabolism ; Mitochondria ; Nuclear Medicine ; Oxidative Phosphorylation ; Protein Isoforms ; RNA, Messenger

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.
Adult ; Alleles ; Carcinogens ; Cytochrome P-450 CYP2E1* ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Digestion ; DNA ; Genetic Predisposition to Disease* ; Genotype ; Humans ; Incidence ; Isoenzymes ; Korea ; Metabolism ; Uterine Cervical Neoplasms*

Direct Black 38, a kind of benzidine-based azo dye, is widely used as a dye for fabric, leather, cotton, cellulosic material, paper, wool, silk, and so on. Benzidine-based azo dyes are proven as a mutagen and linked to bladder cancer. In 1978, Natonal Institute for Occupational Safety and Health recommended that three widely used benzidine-based dyes (Direct Black 38, Direct Blue 6, and Direct Brown 95) should be treated as carcinogens. In this experiment, metabolism of the benzidine-based dye. Direct Black 38 was examined by using an isolated liver perfusion system. To measure the metbolites of Direct Black 38,/ 8.0 micrometer, 30.5 micrometer and 63,3 micrometer of Direct Black 38 was added into the recirculating perfusate of the isolated perfused rat liver. Samples were collected at 0, 10, 20, 30, 60, 90. 120 minute. They were treated with sep-pak and methanol, and the metabohtes were detected and quantified with high performance liquid chromatography (HPLC). Residual non-reactive dye in the perfusate and liver was reduced to benzidine and then analyzed by HPLC. Detected metabolites of ?Direct^-Black 38 were benzidine, N-acetylbenzidine, and N,N'-diacetylbenzidine. The average conentration of benzidine was 0.1 micrometer and this concentration was maintained throughout the experimental period. The average concentration of N-acetylbenzidine was 0.22 micrometer and took the same pattern of benzidine. When 30.5 micrometer of Direct BIact 38 was added to the perfusate, only. N,N'-diacetylbenzidin.e increased slightly with time. From the above results we suggest that only small amount of Dirst Black 38 might be metabolized to benzidine regardless of the s, amount of the Direct Black 38. There are some possible explanations. The liver was damaged during the perparation. And the function of the perfused liver decreased rapidly because adsorbing of dye. The benzidine, acetylbenzidine and diacetylbenzidine metabolized to other metabolites were not detected in this experiment.
Animals ; Carcinogens ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Coloring Agents ; Liver* ; Metabolism* ; Methanol ; Occupational Health ; Perfusion ; Rats* ; Silk ; Urinary Bladder Neoplasms ; Wool

Adult ; Carcinogens ; Epoxy Compounds ; poisoning ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Multivariate Analysis ; Mutation ; drug effects ; Occupational Exposure ; analysis ; Regression Analysis ; Sister Chromatid Exchange ; drug effects

OBJECTIVETo clone differentially expressed cDNA sequences involved in malignant transformation induced by benzo(a)pyrene metabolite dihydroxyepoxy benzo pyrene (BPDE).

METHODThe malignant transformation of human bronchial epithelial cell line 16HBE induced by BPDE in vitro was used as a model for comparing gene expression between the transformed cells and controls. cDNA representational difference analysis (cDNA-RDA) was performed to isolate differentially expressed cDNA fragment in transformed cells. The cDNA fragments were ligated to pGEM-T vector and transformed into JM109 bacteria. The plasmid DNA were sequenced and compared with data in GenBank by BLASTN.

RESULTSFive cDNA sequences were found to be novel ones and were registered in dbest database, which assigned accession numbers in GenBank are BG354691, BG354692, BG354693, BG354694 and BG354695, respectively. Eight of the remaining cDNA sequences showed sequence homology to those previously reported such as ribosomal protein S23, MLN137, ACTN4, transforming growth factor and G protein gene.

CONCLUSIONSThese 13 genes may be involved in BPDE-induced malignant transformation, but their biological characteristics and functions are left to further studies.

Benzopyrenes ; metabolism ; pharmacology ; Carcinogens ; pharmacology ; Cell Transformation, Neoplastic ; chemically induced ; genetics ; Cells, Cultured ; Cloning, Molecular ; DNA, Complementary ; analysis ; drug effects ; DNA, Neoplasm ; analysis ; Gene Expression ; drug effects ; Humans