• Title/Summary/Keyword: Chemical carcinogenesis

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Quantitative and Qualitative Extrapolation of Carcinogenesis Between Species

  • Gold Lois Swirsky;Manley Neela B.;Ames Bruce N.
    • 대한예방의학회:학술대회논문집
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    • 1994.02a
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    • pp.431-438
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    • 1994
  • As currently conducted, standard rodent bioassays do not provide sufficient information to assess carcinogenic risk to humans at doses thousands of times below the maximum tolerated dose. Recent analyses indicate that measures of carcinogenic potency from these tests are restricted to a narrow range about the maximum tolerated dose and that information on shape of the dose-response is limited in experiments with only two doses and a control. Extrapolation from high to low doses should be based on an understanding of the mechanisms of carcinogenesis. We have postulated that administration of the maximum tolerated dose can increase mitogenesis which, in turn. increases rates of mutagenesis and, thus, carcinogenesis. The animal data are consistent with this mechanism, because about half of all chemicals tested are indeed rodent carcinogens, and about 40% of the positives are not detectably mutagenic. Thus, at low doses where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than commonly assumed. In contrast, for high-dose exposures in the workplace, assessment of hazard requires comparatively little extrapolation. Nevertheless. permitted workplace exposures are sometimes close to the tumorigenic dose-rate in animal tests. Regulatory policy to prevent human cancer has primarily addressed synthetic chemicals, yet similar proportions of natural chemicals and synthetic chemicals test positive in rodent studies as expected from an understanding of toxicological defenses, and the vast proportion of human exposures are to natural chemicals. Thus, human exposures to rodent carcinogens are common. The natural chemicals are the control to evaluate regulatory strategies, and the possible hazards from synthetic chemicals should be compared to the possible hazards from natural chemicals. Qualitative extrapolation of the carcinogenic response between species has been investigated by comparing two closely related species: rats and mice. Overall predictive values provide moderate confidence in interspecies extrapolation; however, knowing that a chemical is positive at any site in one species gives only about a 50% chance that it will be positive at the same site in the other species.

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The Cancer-Preventive Potential of Panax ginseng - A Review of Human and Experimental Evidence - (인삼(Panax ginseng) 항암 효과에 관한 문헌고찰 - 실험연구와 역학연구 결과를 중심으로 -)

  • Kim, Joon-Youn;Lee, Duk-Hee;Yun, Taik-Koo;Morgan, Gareth;Vainio, Harri;Shin, Hai-Rim
    • Journal of Preventive Medicine and Public Health
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    • v.33 no.4
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    • pp.383-392
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    • 2000
  • Objective : We have reviewed the potential cancer preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in oriental countries. Data identification and study selection: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-2000) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were also considered. Results : Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. Conclusion : While Panax ginseng C. A. Meyer has shown cancer preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

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The Psychological Impacts of Chemical, Biological and Radiological Disasters (화학, 생물, 방사능 사고의 정신적 영향)

  • Lee, Da Young;Sim, Minyoung
    • Anxiety and mood
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    • v.13 no.1
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    • pp.1-9
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    • 2017
  • We reviewed the scientific literature on psychological effects of Chemical, Biological, Radiological, Nuclear, Explosive (CBRNE) disaster, which is one of the biggest threat to modern society. CBRNE disaster has the potential to cause specific physical symptoms and psychological distress in victims ; moreover, various toxic symptoms and carcinogenesis/mutation would be an important issue. Bioterrorism can cause localized outbreaks of infectious disease or pandemic disaster. Somatization as well as posttraumatic stress symptoms and depression are the characteristic psychological symptoms in CBRNE disaster's victims. CBRNE disasters could lead to large-scale public fear and social chaos due to the difficulties involved in verifying the extent of exposure and unfamiliar area to the common people. In the evacuation process, problems associated with adjustment and conflict between victims and residents should be considered.

A close Relationship between Carcinogenicity and Self-atom Polarizability Index of Polycyclic Aromatic Hydrocarbons and Their Metabolites

  • Park, Byung-Kak;Suh, Man-Chul;Paek, U-Hyon
    • Bulletin of the Korean Chemical Society
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    • v.7 no.3
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    • pp.183-185
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    • 1986
  • Self-atom polarizability were calculated for 17 polycyclic aromatic hydrocarbons and their metabolites by LCAO-MO method and examined the relation with the carcinogenicity. It has been found that ${\pi}_{1.2.4}$, the sum of self-atom polarizability of 1, 2 and 4 positions forming trans-butadiene frame in a compound, agree quite well with the observed carcinogenic activity, and also, ${\pi}_{1.2.4}$ value increase with the metabolic activiting in agreement with the experimental facts that parent carcinogens activated with metabolism. Accordingly, we suggest that the 1, 2 and 4 positions in the carcinogenic compounds play the most important role in the process of chemical carcinogenesis, and also self-atom polarizability, as one of theoretical reactivity indices, is to be used as a measure of carcinogenic activity.

Novel $\delta$-Lactam base Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation I.

  • Park, Bum-Woo;Ryu, Dong-Kyu;Kim, Tae-Kyun;Park, Song-Kyu;Han, Jeong-Hwan;Han, Gyoon-Hee
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.184.1-184.1
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    • 2003
  • HDAC and HAT (histone acetyltransferase) are involved in co-regulation in chromatin remodeling and the functional regulation of gene transcription. Abnormal recruitment of HDAC is related to carcinogenesis. Thus, the identification of potent histone deacetylase (HDAC) inhibitor has been considered as very intriguing approach for development for cancer chemotherapy. More recently, anti-inflammatory activity of SAHA cytokines was reported via reduction of proinflammatory cytokinres in vitro and in vivo. (omitted)

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Effects of Airborne Samples Collected in Yeochun on Gap Junctional Inter cellular Communication in WBF-344 Rat Liver Epithelial Cells (여천공단 일부지역의 대기오염물질이 WBF-344간 상피세포의 Gap Junctional Intercellular Communication에 미치는 영향)

  • 양재만;박재학;김윤신;이영순
    • Journal of Korean Society for Atmospheric Environment
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    • v.13 no.3
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    • pp.207-214
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    • 1997
  • We collected airborne complex mixtures in a industrial area of Yeochun, and examined whether these complex mixtures could affect gap junctional intercellular communication (GJIC) in a cultured WBF-344 rat liver epithelial cells (LEC). Since the reduction of GJIC plays an important role in chemical carcinogenesis, measurement of changes of GJIC is a meaningful method to screen carcinogenicity of these mixtures. High and low volume samples were dissolved in dimethyl sulfoxide (DMSO) and tested. Blank filter extractions were also examined for exclud-ing possible toxicity of filter itself, and TPA (12-O-tetradecanoylphorbol-13-acetate) and DMSO were used as positive and negative control, respectively. When the cells were exposed to samples at concentration below that required to maintain rather than 85% cell viability based on the result of neutral red uptake assay, maximal inhibition of GJIC was observed at 1hr after treatment with both high and low volume samples by scrape-loading dye transfer assay. In fluorescence recovery after photobleaching assay, recovery rates via gap junctions were 33%/min in high volume sample and 62%/min in low volume sample. In together, airborne samples collected in Yeochun inhibited GJIC in a cultured WBF-344 rat LEC. These results suggest airborne samples tested in this experiment may attribute to cause a certain type and degree of cancers in in vivo when exposured for some periods.

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Assessment of the Risk of Exposure to Chemical Carcinogens

  • Purchase, Iain F.H.
    • Toxicological Research
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    • v.17
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    • pp.41-45
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    • 2001
  • The methods used for risk assessment from exposure to chemicals are well established. in most cases where toxicity other than carcinogenesis is being considered, the standard method relies on establishing the No Observed Adverse Effect Level (NOAEL) in the most sensitive animal toxicity study and using an appropriate safety factor (SF) to determine the exposure which would be associated with an acceptable risk. For carcinogens a different approach is used because it has been argued there is no threshold of effect. Thus mathematical equations are used to extrapolate from the high doses used in ani-mal experiments. These methods have been strongly criticised in recent years on several grounds. The most cogent criticisms are a) the equations are not based on a thorough understanding of the mechanisms of carcinogenesis and b) the outcome of a risk assessment based on such models varies more as a consequence of changes to the assumptions and equation used than it does from the data derived from carcinogenicity experiments. Other criticisms include the absence of any measure of the variance on the risk assessment and the selection of default values that are very conservative. Recent advances in the application of risk assessment emphasise that measures of both the exposure and the hazard should be considered as a distribution of values. The outcome of such a risk assessment provides an estimate of the distribution of the risks.

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Effect of Fiber-Rich Sea Mustard Feeding on AOM-Induced Colon Aberrant Crypt Formation and Colonic Cell Proliferation in Sprague Dawley Rats (미역의 섭취가 화학적으로 유도된 쥐의 대장암화 표지자인 Aberrant Crypt 형성 및 상피세포 분열에 미치는 영향에 관한 연구)

  • 이은주;성미경
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.3
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    • pp.535-539
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    • 2001
  • The modulating effect of feeding sea mustard (Undarina pinnatifida), a fiber-rich seaweed, during initiation and post-initiation phases of colon carcinogenesis was investigated in Sprague Dawley rats. Four groups of animals were exposed to the two weekly injections of a chemical carcinogen, azoxymethane (AOM). Animals were placed on diet containing 15% sea mustard during initiation. post-initiation or initiation+post-initiation phase of carcinogenesis for 10 weeks, and colonic aberrant crypt formation and cell proliferation were compared to those of rats fed semi-synthetic control diet. Results showed that sea mustard feeding significantly reduced the numbers of both aberrant crypts and aberrant crypt foci. Also, labeling indices and proliferation zones were significantly reduced in the colon of the rats fed sea mustard diets. These results indicate that the diet containing sea mustard may decrease the risk of colon cancer development, and a part of such effect may be mediated through both the blocking of initiation and the suppression of cell proliferation in the colonic crypts, although precise mechanisms should be further examined.

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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.

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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