• 대한화학회지
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• 제24권3호
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• pp.225-232
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• 1980

化學發癌物質인 縮合炭化水素, 헤테로고리化合物 그리고 디메틸아미노아조벤젠 및 그의 유도체들의 電子狀態를 HMO로 調査하고 그들의 發癌活性을 論議하였다. K-領域의 두 原子와 그의 이웃한 L-領域의 原子들의 親核反應의 프론티어 전자밀도의 合의 값이 0.5 以上인 化合物들은 發癌活性에 있어서 實驗結果와 一致함을 알았다. 따라서 K-領域과 L-領域이 發癌作用의 첫단계로서 化學發癌物質과 生體成分과의 結合이 얻어진다는 것이 보고되어 있는 分子錯物의 形成에 重要한 役割을 한다고 생각한다.

• Toxicological Research
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• 제23권3호
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• pp.189-196
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• 2007

Cytochrome P450 (P450) enzymes are the major catalysts involved in the biotransformation of various drugs, pollutants, carcinogens, and many endogenous compounds. Most of chemical carcinogens are not active by themselves but they require metabolic activation. P450 isozymes playa pivotal role in the metabolic activation. The activation of arylamines and heterocyclic arylamines (HAAs) involves critical N-hydroxylation, usually by P450. CYP1A2 plays an important role in these reactions. Broad exposure to many of these compounds might cause carcinogenicity in animals and humans. On the other hand, P450s can be also involved in the bioactivation of other chemicals including alcohols, aflatoxin B1, acetaminophen, and trichloroethylene, both in humans and in experimental animals. Understanding the P450 metabolic activation of many chemicals is necessary to develop rational strategies for prevention of their toxicities in human health. An important part is the issues of extrapolation between species in predicting risks and variation of P450 enzyme activities in humans.

• 한국환경보건학회지
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• 제44권2호
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• pp.160-168
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• 2018

Objectives: The purposes of the study were to investigate hazardous pollutant emissions changes among group 1 carcinogens. The emissions characteristics were compared with national cancer registration statistics. Methods: A survey of group 1 carcinogen hazardous pollutant emissions (trichloroethylene, benzene, vinyl chloride, formaldehyde, 1,3-butadiene, ethylene oxide, chromium and its compounds, 3,3'-dichloro-4,4-diaminodiphenylmethane, chloromethyl methyl ether, arsenic and its compounds, cadmium and its compounds, o-toluidine) was conducted through a homepage for 2001-2015. The emission of hazardous chemicals and the cancer trend analysis for 2001-2015 were performed using the Korean statistical information service through its homepage as a reference. Results: Emissions of more than 95% of the substances listed as group 1 carcinogens over the last five years were made up of trichloroethylene, benzene, vinyl chloride, formaldehyde, 1,3-butadiene, and ethylene oxide. As a result of the comparison of emission results and cancer incidence rates, carcinogen pollutant emissions showed a tendency to decrease continuously. In addition, the incidence of cancer tended to increase, but showed a tendency to decrease from 2012. Conclusion: The results indicate hazardous pollutant emissions have continued to increase. However, no association between emissions and health effects was shown and more research is needed.

• 한국산업보건학회지
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• 제28권1호
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• pp.1-17
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• 2018

Objectives: This research is part of a study to be conducted over five years starting from 2017 by the Ministry of Environment on the development of technologies to evaluate the impact of chemical accidents on the human body. Methods: For this research, a five-stage specific study method was developed. Results: In brief, the developed health risk assessment method can be summarized as follows. First, a health risk assessment system was built based on the guidelines set forth by the USA NRC/NAS. Second, based on the disease manifestation theory, the health risk assessment method was divided into 1) a carcinogenic health risk assessment method focused on all carcinogens except non-genotoxic carcinogens and 2) a non-carcinogenic health risk assessment method focused on noncarcinogens including non-genotoxic carcinogens. Third, the detailed contents of the health risk assessment method were developed in four stages(hazard identification, dose-response assessment, exposure assessment, and risk determination) through theoretical consideration of the assessment of the level of health risk related to chemical exposure. Finally, a health risk assessment methodology, classified into stages to address acute, subacute/subchronic, and chronic conditions was developed after considering the physicochemical behavior of hazardous chemicals upon implementation of countermeasures after a chemical accident. Conclusions: A method to evaluate the health risks related to toxic chemicals generated by chemical accidents was developed. This study was performed with the purpose of developing a mathematical health risk assessment method to evaluate the health effects of exposure to hazardous chemicals upon implementation of emergency countermeasures after chemical accidents.

• 한국환경성돌연변이발암원학회지
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• 제18권1호
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• pp.1-8
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• 1998

Chemoprevention refers to the use of non-toxic chemical agents to prevent the neoplastic development by inhibiting, delaying, or reversing a multi-stage carcinogenesis. The primary goal of chemoprevention research is to identify or produce effective agents and strategies for clinical trials for applications to normal or high risk human populations. A large number of compounds have been tested for their possible chemopreventive activities, and it is of interest to note that many of them are naturally occurring substances. Thus, a variety of plant and vegetable constituents, particularly those included in our daily diet, have been found to possess substantial protective properties against experimental carcinogenesis. These substances, collectively known as dietary phytochemicals, exert their chemopreventive effects by influencing specific step(s) of multi-stage carcinogenesis: some inhibit metabolic activation or enhance detoxification of carcinogens, others interfere with covalent interactions between ultimate eloctrophilic carcinogens and the target cell DNA and still others may exert anti-promoting or anti-progressing effects. Mechanism-based interventions by use of safe dietary phytochemicals may provide one of the most practical and promising cancer chemopreventive strategies.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 국제심포지움
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• pp.1-19
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• 2002

It is well established that the initiating event in chemical carcinogenesis is the binding of reactive carcinogens to DNA. Thus, a number of analytic methods have been developed for determining levels of carcinogen-DNA adducts in humans as a marker of individual exposure and, potentially, of risk for cancer development. In addition, reactive carcinogens also bind to protein suggesting protein adducts can be used as a surrogate for DNA adducts in some situations. We have developed monoclonal and polyclonal antibodies to carcinogen-DNA and protein adductis and highly sensitive ELISA and immunohistochemical assays for determining levels of adducts in human tissues. These studies have demonstrated higher levels of adducts in those with higher exposure as a result of workplace, dietary, chemotherapy, environmental of lifestyle (smoking) exposures. Elevated levels of adducts have been found in lung and liver cancer cases compared to controls. We have also used DNA adducts to determine efficacy of an antiosidant vitamin intervention. DNA adduct studies have demonstrated very different levels of damage in those with similar exposure levels. These interindividual differences are likely the result genetic differences in capacity to activate carcinogens, detoxify reactive intermediates and repair DNA adducts once formed. We are currently investigating the relationship between polymorphisms in a number of these genes to determine their relationship to adduct levels as well as their ability to confer increased risk for cancer development. The ability to identify high risk individuals will allow the targeting of screening and preventive strategies to those most likely to benfit.

• 대한안전경영과학회지
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• 제12권3호
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• pp.107-119
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• 2010

The aim of this study was to compare the carcinogen classification systems of developed countries or global organizations with domestic system under Industrial Safety and Health Act (ISHA). We selected the representative institutions which had carcinogen classification system such as International Agency for Research on Cancer (IARC), National Toxicological Program (NTP), Environmental Protection Agency (US-EPA), American Conference of Governmental Industrial Hygienists (ACGIH), and European Union (EU). We collected the carcinogen lists issued by 5 institutions, and merged by CAS number of each chemical with Microsoft Access 7.0. We found that confirmed human carcinogens, probable human carcinogens and possible human carcinogens were 34, 179, and 252, respectively. All of the institutions classified chemicals as 2 (NTP), 3 (EU) or 5 (IARC, ACGIH, US-EPA) categories based on the weight of scientific evidences for carcinogenicity and periodically updated the carcinogen list by regular procedure. However, a total of 90 chemicals could be classified as carcinogen under ISHA in Korea. There was no procedure or system which periodically update the carcinogen lists. In addition, the status of carcinogen classification according to regulation was confused. In conclusion, these findings suggest that the carcinogen classification and management system should be amended by consideration of systems of advanced institutions and the domestic regulation system.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.474-478
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• 1999

Modulation of unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) after exposure to various chemical carcinogens was investigated in the primary rat hepatocytes. Unscheduled DNA synthesis was induced by treatment of such direct acting carcinogens as methly methanesulfonate (MMS) and ethyl methanesulfonate (EMS) or procarcinogens including benzo(a)pyrene (BaP) and 7, 12-dimethylbenz(a)anthracene (DMBA). Unscheduled DNA synthesis was determined by measuring [methyl-3H]thymidine radioactivity incorporated into nuclear DNA of hepatocytes treated with carcinogens in the presence or absence of DHEA. Hydroxyurea $(5{\times}10^{-3} M)$was added to growth medium to selectively suppress normal replication. DHEA at concentrations ranging from $(1{\times}10^{-6} M)$ to$(5{\times}10^{-4} M)$ did not significantly inhibit unscheduled DNA synthesis induced by either MMS $(1{\times}10^{-4} M)$ or EMS $(1{\times}10^{-2} M)$. In contrast, DHEA-significantly inhibited unscheduled DNA synthesis induced by BaP $(6.5{\times}10^{-5} M)$ and DMBA.$(2{\times}10^{-5} M)$. DHEA-induced hepatotoxicity in rats was examined using lactate dehydrogenase (LDH) release as an indicator of cytotoxicity. DHEA exhibit no significant increase in LDH release compared with the control at 18 h. These data suggest that nontoxic concentration of DHEA does not affect the DNA excision repair process, but it probably influence the enzymatic system responsible for the metabolic activation of procarcinogens and thereby decreases the amount of the effective DNA adducts formed by the ultimate reactive carcinogenic species.

• Toxicological Research
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• 제18권3호
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• pp.293-300
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• 2002

Chemical carcinogen-induced alteration of aldehyde metabolic enzymes were examined in clone 9 cell. Diethylnitrosamine (DENA), N-nitrosoethylurea (NEU) and N-nitrosomorpholine (NNM) were wed as model carcinogens. Changes in enzyme activities by repetitive treatment of DENA, NEU or NNM were analyzed in terms of specific activities and activity stainings of the enzymes on the gel. Upon treatment of DENA, lipid peroxide level increased upto 10 fold, indicating strong oxidative stress state of the cell. Notable enhancement of ADH and ALDH activity occurred after DENA treatment, while glutathione-S-transferase activity was slightly increased. Furthermore, about 2.5 fold higher superoxide dismutase (SOD) activity was detected during deactivation of catalase (CAT) activity by repetitive treatment of DENA. However in NEU-treated cell, about 2.3 fold higher ALDH activity was found while ADH activity was slightly increased. Notable increase CAT and SOD could also be found. In contrast, maximum 3.5 fold higher CAT activity occurred during SOD deactivation in NNM-treated cell. These results suggest that there might be different enzymatic responses in relation to cell protection against DENA, NEU or NNM.

• Bulletin of the Korean Chemical Society
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• 제1권2호
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• pp.71-73
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• 1980

The electronic structure of photo-skinsensitizing psoralens has been investigated by the FMO method. On the basis of theoretical calculations, optimum value of indices (Ft=0.33) has been proposed which corresponds to the sum of frontier electron density. The results indicate that this index is closely correlated with photo-skinsensitizing carcinogenic activity. The formations of molecular complexes between DNA and photo-skinsensitizing carcinogens is discussed in terms of charge transfer interactions.