• Title/Summary/Keyword: chemical carcinogen

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Development of in vitro Short-term Carcinogenicity Test Method and its Mechanism of Action

  • Cho, Dae-Hyun;Kim, Jun-Gyou-;Ahn, Mi-Young;Park, Mi-Kyung-;Moon, Byung-Woo;Moon, Hwa-Hwey;Lee, Byung-Mu-
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.336-336
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    • 1994
  • In order to develope the in vitro short term screen-ing method for carcinogen, we studied a purification method for thymine glycol in oxidaized DNA. Thymine glycol (5,6-dihydroxy-5, 6-dihydrothymine) is the major stable radiolysis poduct in thymine by chemical oxidants and ionzing radiation and it is a useful biomarker among oxidized DNA adducts, related with carcinogenests. Standard thymine glycol was prepared by oxidation of 〔$^3$H〕 thymine with KMnO$_4$ followed by purification with HPLC-LSC system and it was assayed by TLC and gas chromatography-MSD. 〔$^3$H〕 DMA adducts was isolated from E. coli (wild type ) treated with oxidative agents such as benzo(a)pyrene, adriamycin, aflatoxin B$_1$ and KBrO$_3$. These oxidative agents generated free radicals in cells by oxidative metabolism. As a result, thymine glycol was produced in cultured E. coli by four chemicals. This result shows that this methodology should be useful tool in screening oxidative carcinogen.

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Effects of Corn Oil, Perilla Oil, Sardine Oil Diet on the Hepatic Glutathione S-transferase(GST-P) Positive Foci and Glutathione Related Enzyme System in Carcinogen Treated Rats (옥수수유, 들깨유, 정어리유의 급여가 발암물질의 투여한 쥐 간의 Glutathione S-transferase(GST-P) 양성결절과 Glutathione 관련 효소계에 미치는 영향)

  • Kim, Kyung-Min
    • The Korean Journal of Food And Nutrition
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    • v.23 no.2
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    • pp.276-284
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    • 2010
  • The effects of different dietary fatty acids on the hepatic glutathione S-transferase(GST-P) positive foci and glutathione related enzyme system were investigated in carcinogen treated rats. Weaning male Sprague Dawley rats were divided into three groups and fed the diets of 15% corn(CO), perilla(PO), and sardine oil(SO), respectively. Hepatocellular carcinogenesis was initiated with diethylnitrosamine(DEN) and then fed the diet containing 0.02% 2-acetylaminofluorene(2-AAF) followed by 0.05% phenobarbital for 10 weeks. The hepatic tissues were homogenized and centrifugated to prepare microsomal and cytosolic fractions. The enzyme activities of hepatic glutathione S-transferase(GST), glutathione reductase(GR), and glutathione peroxidase(GPx) were determined from cytosolic fractions. The number of GST-P hyperplastic nodules was the highest in corn oil group at 6th week, the early stage of hyperplastic nodule formation. GST activities were increased significantly by carcinogens in all dietary groups after 6th wk. GR activities followed the same trend as GST activities. GPx activities were decreased by carcinogens in all dietary groups at 10th week. In this experiment, corn oil diet may have promotive effect on hyperplastic nodule formation during the early promotional stages of chemical carcinogenesis.

EXPRESSION OF PROTEIN KINASE C ISOFORMS IN CHEMICAL CARCINOGEN-INDUCED NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS (화학적 발암화에 따른 Protein Kinase C의 발현 변화)

  • Byeon, Ki-Jeong;Hong, Lak-Won;Kim, Chin-Soo
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.23 no.4
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    • pp.295-305
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    • 2001
  • Protein kinase C (PKC) is known to play a pivotal role in neoplastic transformation cells and its high expression is often found in a variety of types of tumors including oral cancer. While PKC is associated with the altered signal transduction pathway of the tumor cells, it is still unclear which isoform is involved in the carcinogenesis process. Since the cellular distributions and the roles of PKC are isoform-specific, it is very important to identify the specific target molecules to improve our understanding of the carcinogenesis processes. Thus, the present study attempted to perform chemical carcinogen-induced neoplastic transformation of human epithelial cells and analyze the specific isoform of PKCs involved in the cellular transformation. The study analyzed overall PKC responses upon MNNG(N-Methyl-N'-nitro-N-nitroso guanidine) exposure with [$^3H$] PDBu binding assay. PKC translocation was observed at high doses of MNNG treatment in the presence of extracellular calcium. Such effects were not observed in the absence of extracellular calcium. Translocational effects with exposure of MNNG was further enhanced in the presence of hydrocortisone. The result suggests that the type of PKC involved may be $Ca^{2+}$-dependent classical isoform and steroid hormone enhances PKC activation. Among cPKC isoforms examined, only $PKC-{\alpha}$ and r showed significant translocation of protein levels from cytosolic fraction to membrane fraction, as analyzed by immunoblot. $PKC-{\varepsilon}$ in nPKC class showed an inch·eased translocation, but other forms in this class did not show the effect. None of isoforms in aPKC class was affected by MNNG treatment. The study demonstrated that there was a certain specificity in the patterns of isoform induction follwong chemical carcinogen exposure and helped identify all the types of PKC isoforms expressed in human epithelial cells. It was revealed that PKC isoforms were activated in an early resonse to chemical carcinogen, suggesting that PKC be associated with carcinogenesis process from an early stage in this particular cell system. The study will contribute to improving our understanding of chemical-induced carcinogenesis in human cells and may provide a scientific basis to introduce the specific PKC inhibitors as an anticancer drug of epithelial cell-origin cancers including oral cancer.

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Basic Concepts of Western Medicine Toxicology and $LD_{50}$ in Herbal Drugs (서양의학 독성학의 기본적 개념 및 한약의 $LD_{50}$)

  • Park Yeon-Chul;Lee Sun-Dong;Park Kyoung-Sik
    • Journal of Society of Preventive Korean Medicine
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    • v.3 no.2
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    • pp.91-100
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    • 1999
  • Today, toxicology is used for many purpose, in many fields. Classification of special toxic effect is related next 4 important principles. 1. The chemical substance must move to target organ or tissue that can induce Biological effect. For this movement, we have to understand the physical-chemical characteristic of substance, and the rout of absorption, metabolism, diffusion and excretion of toxic substance. 2. Every biological effect that induced by chemical substance is not harmful. For example, some specific chemical substance is not harmful in liver enzyme system. 3. The strength of biological effect induced by chemical substance is deep related with dose. Nearly all substance is not effective below the specific dose, and it may toxic to death over the specific dose. It is the 'Dose - response relationship' But carcinogen may toxic whether it is law dose or not. 4. The information that was obtained by experimental animal test, could have to adapt in human biology. Because biological effect of chemical substance could be different in every biological species. In past, drugs was obtained by animal or plants. But in the future, it could be obtained by biochemistry, and genome project. Therefore, in Oriental medicine, research and approach is needed at this time, and have to develop new method of experience in toxic method.

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Study on Measurement of Carcinogen-DNA adducts in exfoliated urothelial cells among workers by 32P-postlabelling methods (근로자의 뇨중 상피세포에서 32P-postlabeling에 의한 발암물질의 DNA adducts측정방법에 대한 연구)

  • Lee, Jin Heon;Roh, Jaehoon;Talaska, Glenn
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.10 no.1
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    • pp.1-17
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    • 2000
  • Carcinogen-DNA adduct analysis has potential for biomonitoring the earliest effects of exposure to many chemical carcinogens. They are the covalent reaction products of electrophiles and nucleophilic sites on DNA and the initial damage to DNA induced by many carcinogens. So many researchers begin to use them as biomarker for monitoring the earliest exposure of carcinogens and develop the effective analytical techniques about them. Randerath, Gupta and coworkers(1981, 1982) has also developed a $^{32}P$-postlabelling method as one among them. A major project for biomonitoring workers with carcinogen-DNA adducts is to develop non-invasive samples instead of tissues of target organs such as baldder and lung. This study use the exfoliated urothelial cells in urine for examine benzidine-DNA adducts. The content of exfoliated urothelial cells is not enough to significantly measure DNA content with spectrophotometer, and require the another way. So firstly washing the collected cells with PBS and 70% ethanol and centrifuge them for removing the crystals in urine, which block the isolation of DNA adducts. And then, measure the total nucleotide after $^{32}P$-postlabelling for calculating RAL. $[{\gamma}-^{32}P]ATP$ using for $^{32}P$-postlabelling, can synthesize with $[^{32}P]H_3PO_4$, and reagent and enzyme mixture (RM, EM), which is very economic in case of requiring a lot of them. Chromatography was composed of two steps. First step was to separate adduct ones from unadducted nucleotide, and secondary step was separate each adduct, which were performed with 4 kinds of solvents and different directions on TLC. With this procedure, we measure the DNA adducts in exfoliated urothelial cells of workers who were employed in benzidine and benzidine-dye company. RAL of adducts were $89.0{\times}10^7$ and $57.0{\times}10^7$ in them. In conclusion, we can significantly measure the DNA adduct in exfoliated urothelial cells by using the above $^{32}P$-postlabelling procedures, and use them to be biomonitoring workers who exposed carcinogens.

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Application of Molecular Orbital Theory to Biological Chemistry (Ⅰ). Correlation between the Electronic State of Chemical Carcinogens and their Carccinogenicity (分子軌道論의 現物化學에의 應用 (第1報). 化學發癌物質의 電子狀態와 發癌性과의 相關關係)

  • Byung-Kak Park
    • Journal of the Korean Chemical Society
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    • v.24 no.3
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    • pp.225-232
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    • 1980
  • The electronic states of chemical carcinogens such as polycyclic aromatic hydrocarbons, heterocyclic compounds and dimethylaminoazobenzene (DAB) and its derivatives were examined and discussed for their carcinogenicity by means of simple Huckel method.The compounds which are 0.5 or more in the value of the sum of frontier electron density for nucleophilic reaction of the two atoms of K-region and that of the atom of L-region in the proximity of K-region were found to be agreed well with experimental results for carcinogenic activity. It is therefore suggested that both the K-region and the L-region play an important role in the formation of the molecular complex which was shown to be obtained in the combination of chemical carcinogen with cellular component in the first step of carcinogenesis.

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Methodology of Human Cancer Risk Assessment for Chemical Carcinogens (화학 발암물질에 대한 인체 암 위해성 평가)

  • Lee, Byung-Mu
    • Toxicological Research
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    • v.8 no.2
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    • pp.317-329
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    • 1992
  • Fifty chemicals are currently classified as human carcinogens based on epidemiologic and animal data. Humans are daily exposed to them from various sources of exposure via inhalation, dermal contact and oral ingestion. To reduce cancer risk to man, these human carcinogens should be appropriately regulated and monitored environmentally or biologically for routine human cancer risk assessment. A number of mathematical risk assessment models have been introduced, but any realistic and relevant model system is not available for humans. A mechanistic process for human cancer risk assessment was comprehensively reviewed and problems were also discussed. Here, a new conceptual approach using epidemiology and biological human monitoring was suggested for the most relevant method to study human cancer risk assessment.

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Development of a Detailed Chemical Kinetic Reaction Mechanism of Surrogate Mixtures for Gasoline Fuel (가솔린 연료를 위한 대용혼합물의 상세한 화학반응 메카니즘 개발)

  • Lee, Ki-Yong
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.33 no.1
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    • pp.46-52
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    • 2009
  • The oxidation of surrogate mixtures for gasoline fuel was studied numerically in perfectly stirred reactor(PSR) to develope the needed detailed reaction mechanism. The reaction mechanism was assembled with the mechanisms for the oxidation of iso-octane or kerosene. It was shown that the reaction model predicted reasonably well the concentration profiles of fuel and major species reported in the literature. As the addition of kerosene into iso-octane as fuel was increased, the concentrations of $C_2H_2$ and benzene became high. Especially benzene known as a carcinogen appeared at a very high concentration in the flue gases.

Chemical Use and Associated Health Concerns in the Semiconductor Manufacturing Industry

  • Yoon, Chungsik;Kim, Sunju;Park, Donguk;Choi, Younsoon;Jo, Jihoon;Lee, Kwonseob
    • Safety and Health at Work
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    • v.11 no.4
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    • pp.500-508
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    • 2020
  • Background: Research on the status of many chemicals used in the semiconductor industry is needed. The purpose of this study was to describe the overall status of chemical use in the semiconductor industry in Korea and to examine it from a health perspective. Methods: Data on the status of chemical use and safety data sheets at 11 of 12 major semiconductor workplaces in Korea were collected. The number of chemical products and chemical constituents, quantities of chemicals, and trade secret ingredients used, as well as the health hazards were examined. Results: On average, 210 chemical products and 135 chemical constituents were used at the surveyed workplaces. Among all chemical products, 33% (range: 16-56%) contained at least one trade secret ingredient. Most of the trade secret ingredients were used in the photolithography process. Several carcinogens, including sulfuric acid, chromic acid, ethylene oxide, crystalline silica, potassium dichromate, and formaldehyde were also used. Only 29% (39 of 135) of the chemical constituents had occupational exposure limits, and more than 60% had no National Fire Protection Association health, safety, and reactivity ratings. Based on the aforementioned results, this study revealed the following. First, many chemical products and constituents are being used in the semiconductor industry and many products contained trade secret ingredients. Second, many products contained significant amounts of carcinogenic, mutagenic, and reproductive toxicant materials. Conclusion: We conclude that protecting workers in the semiconductor industry against harm from chemical substances will be difficult, due to widespread use of trade secret ingredients and a lack of hazard information. The findings of the status of chemical use and the health and safety risks in semiconductor industry will contribute to epidemiological studies, safe workplace, and worker health protection.

Survey of nitroso-compounds level derived from additives in metal-working fluids (유통 수용성 금속가공유 중 니트로 화합물 함유 실태)

  • Yang, Jeong Sun;Choi, Jin Hee;Choi, Seong Bong;Lee, Jong Han
    • Analytical Science and Technology
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    • v.20 no.4
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    • pp.268-278
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    • 2007
  • Nitrite which can be derived from water for dilution of metal working fluid can induce nitroso compounds which can be classified as carcinogen, if it co-exists with ethanolamines added for pH control in metal working fluid. The survey of nitrite, nitrate and nitroso-compounds level in 42 metal-working fluids collected from 17 factories was done by ion chromatography and gas chromatography with mass detector. Diluted metal working fluid showed higher level of nitrite and nitrate compared with raw fluid. Nitrite was detected in 11 (52%) samples among 21 diluted solution. Three (14%) samples showed over German recommendation level ($20{\mu}g/mL$).N-nitrosodiethanolamine(NDELA) was detected in 18 samples among 21 diluted solution. Seven (33%) samples showed over German recommendation level ($5{\mu}g/mL$). The concentration of NDELA was correlated with nitrite ion ($R^2=0.453$, n=19).