• 대한화학회지
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• 제24권4호
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• pp.280-287
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• 1980

發癌物質과 DNA 鹽基雙間의 分子錯物形成에서 可能性있는 配置(orientation)를 決定하였다. 아데닌-티민 염기쌍에서는 티민쪽에서, 구아닌-시토신 염기쌍에서는 구아닌쪽에서 分子錯物을 形成한다.

• 대한약리학회지
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• 제28권2호
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• pp.213-222
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• 1992

Benzopyrene (BP), 7,12-dimehyl benzanthracene (DMBA), nitrosomethyl urea (NUMU) 및 nicotine과 같은 발암성 화학물질들이 바이러스 감염된 vero 세포의 단층 세포 배양에서 I형 단순성포진 바이러스 (HSV-1)의 복제, 세포융해, DNA합성 및 단백질 합성에 미치는 효과를 관찰하였다. 1. BP와 DMBA는 HSV-1의 복제와 세포융해작용을 유의성있게 억제하였으나 nicotine과 NMU는 별로 억제하지 않았다. 2. 모든 발암성 화학물질은 바이러스의 DNA합성을 억제하지 못하였지만 새로 합성되는 후손바이러스 DNA로 부터 표현되는 gamma 단백질의 표현은 BP와 DMBA에 의해서 현저하게 억제되었다. 그러나 모든 발암성 화학물질은 바이러스의 alpha 및 beta 단백질의 합성은 억제하지 못하였다. 이상의 결과로 보아 발암성화학물질이 존재하고 있는 배지내에서 새로 합성되는 바이러스의 DNA로 부터 표현되는 gamma 단백질의 결함이 있음을 알 수가 있었으며 이같은 개념은 발암화학물질의 존재하에서 바이러스의 DNA와 단백질이 거의 정상적으로 합성됨에도 불구하고 바이러스의 복제가 일어나지 않는다는 사실이 뒷받침해주고 있다.

• Toxicological Research
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• 제34권4호
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• pp.281-290
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• 2018

Exposure to chemical agents is an inevitable consequence of modern society; some of these agents are hazardous to human health. The effects of chemical carcinogens are of great concern in many countries, and international organizations, such as the World Health Organization, have established guidelines for the regulation of these chemicals. Carcinogens are currently categorized into two classes, genotoxic and non-genotoxic carcinogens, which are subject to different regulatory policies. Genotoxic carcinogens are chemicals that exert carcinogenicity via the induction of mutations. Owing to their DNA interaction properties, there is thought to be no safe exposure threshold or dose. Genotoxic carcinogens are regulated under the assumption that they pose a cancer risk for humans, even at very low doses. In contrast, non-genotoxic carcinogens, which induce cancer through mechanisms other than mutations, such as hormonal effects, cytotoxicity, cell proliferation, or epigenetic changes, are thought to have a safe exposure threshold or dose; thus, their use in society is permitted unless the exposure or intake level would exceed the threshold. Genotoxicity assays are an important method to distinguish the two classes of carcinogens. However, some carcinogens have negative results in in vitro bacterial mutation assays, but yield positive results in the in vivo transgenic rodent gene mutation assay. Non-DNA damage, such as spindle poison or topoisomerase inhibition, often leads to positive results in cytogenetic genotoxicity assays such as the chromosome aberration assay or the micronucleus assay. Therefore, mechanistic considerations of tumor induction, based on the results of the genotoxicity assays, are necessary to distinguish genotoxic and non-genotoxic carcinogens. In this review, the concept of threshold of toxicological concern is introduced and the potential risk from multiple exposures to low doses of genotoxic carcinogens is also discussed.

• Bulletin of the Korean Chemical Society
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• 제6권2호
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• pp.103-107
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• 1985

Quantum chemical calculations were carried out to explain how the electronic states of some series compounds vary with metabolic activation. Compounds studied included aromatic amines and amides, polycyclic hydrocarbons, and a few alkylating agents that do not require metabolic activation. The 1, 2 and 4 positions forming the trans-butadiene frame of a molecule, henceforth referred to as "the trans 1, 2, 4 region", have seen to be important positions for the prediction of carcinogenic activity of these compounds. It is also evident that their electrophilic properties increase with metabolic activation. That is the sum of ${\pi}$-electron densities of the trans 1, 2, 4 region in the lowest unoccupied molecular orbital (LUMO) has been found to increase in the order of precarcinogens < proximate-ones < the carbocation ultimate-ones. This is consistent with the fact that chemical carcinogens become more strongly electrophilic with activating. This region not only provides a unified view of structurally diverse carcinogens, but also predicts uniformity in their reactive sites. Accordingly, we suggest that an understanding of the trans 1, 2, 4 region would be helpful in elucidating the mechanism of carcinogenesis.

• BMB Reports
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• 제28권6호
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• pp.504-508
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• 1995

The electrophoretic patterns of plasma membrane surface proteins of normal rat liver cells and rat hepatomas were compared in 10% non-denaturing and 7-15% gradient non-denaturing gel. Chemical carcinogens, 2-Me DAB (2-methyl-4-dimethylaminoazobenzene) and DENA (diethylnitrosamine), were used to induce hepatoma in rats. One protein which disappeared in hepatoma was identified in normal rat liver by non-denaturing gel electrophoresis. Rabbit antisera were raised against this specific protein, and the protein was purified by Sephacryl S-200 column and immunoaffinity chromatography using the purified antibody. The purified protein showed two bands of molecular weights approximately 50 $kD_{\alpha}$ and 52 $kD_{\alpha}$ by SDS-polyacrylamide gel electrophoresis, which reacted specifically with the antibody. However only one band was observed in non-denaturing gel and also in isoelectric focusing with a pI value of 6.6. This study showed the existence of an unique protein on the plasma membrane surface of normal rat liver cells which disappeared in rat hepatomas induced by chemical carcinogens.

• Toxicological Research
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• 제8권2호
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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.

• Journal of Acupuncture Research
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• 제17권3호
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• pp.151-167
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• 2000

Objective : The aim of this study is to determine the antimutagenic effect and genetic safety of Buthus martensi Karsch aqua-acupuncture solution(BMKAS) against various chemical carcinogens. Method : Ames(Salmonella typhimurium) test and Rec assay(Bacillus subtilis) were used as indicators for DNA damage and antimutagenesis. Furthermore, the levels of umu operon expression by measuring the ${\beta}$-galactosidase activity wete monitored with the SOS umu test using S. typhimurium 1535 containing plasmid pSK1002. And the host-mediated assay was used to investigate the mutagenicity and antimutagenicity of BMKAS inducing various chemical carcinogens after the activation with in vivo metabolic systems. Results : From the results, BMKAS did not atfect DNA of S. typhimurium and B. subtilis strains and showed no mutagenicity at the all concentrations of tested solution. Furthermore BMKAS dose-dependently protected the mutagenecity by AF-2, 2-AA and B[a]P. These phenomena was also similar to that after metabolic activation of BMKAS in in vivo system. Conclusion : These results suggested that BMKAS did not show the mutagenicity and protected the mutagenesis against various chemical carcinogens by four different methods used in this study.

• 한국산업보건학회지
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• 제21권1호
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• pp.40-48
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• 2011

This study was intended to resolve problems caused by different classification criteria and management methods of carcinogenicity, which have made industrial safety & health institutions and business employers difficult to execute projects or to carry out occupational safety and health related works, and have affected how civic groups perceive carcinogens. The content of this study contained the comparison of management and categorization standards for carcinogens between Korea and other countries as well as the current carcinogenicity-related information supply status of each professional institution. Furthermore, this research examined the current state of supplying information on carcinogenicity among major institutional information supply according to the categorization standard for carcinogens by UN GHS, Ministry of Employment and Labor in Korea(KMoEL), and GHS MSDS provided by Korea Occupational Safety & Health Agency(KOSHA). Now, professional agency provide 927 kinds of IARC, 237 kinds of NTP, 351 kinds of ACGIH and 1,006 kinds of EU ECHA information on carcinogenic agents. KMoEL provides carcinogenicity-related information of 58 chemical agents in accordance with the category of carcinogens guided by ACGIH. KOSHA offers 13,232 kinds of GHS MSDS information including 2,484 carcinogenic substances. Therefore, carcinogenicity-related information of chemical substances, which are not available on the existing GHS MSDS DB, should be updated for the future reference.

• 한국환경성돌연변이발암원학회지
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• 제9권1호
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• pp.1-12
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• 1989

특정 발암원의 조직특이성 암유발기전을 연구하기 위하여 DMBA의 구강투여 또는 NMU의 동맥주입에 의하여 유암이 유도되는 실험모델을 대상으로 선택하였다. 본 실험에서는 화학적 발암원의 유암유발기전에 미치는 숙주인 흰쥐의 연령효과를 아울러 비교분석하였으며, 특히 발암원의 조직내 활성화, 불활화 및 해독 그리고 DNA 손상과 수성등의 변화를 구명하였다. 유암의 발생율은 1년생 흰쥐보다 생후 50일 흰쥐에서 현저하게 높았다. 특정조직의 선택적 발암기전을 설명하는 기전의 일환으로 조직 DNA의 특정 발암원에 의한 공유결합성 지표(covalent binding index, CBI)를 발암원의 활성화 기전 지표로는 cytochrome P450의 함량을 반면 불확화의 지표로는 glutathione S-transferase와 peroxide의 활성을 비교하였다. 조직의 CBI는 생후 50일군의 유선조직이 DMBA나 NMU에 대하여 간조직보다 유의하게 높았으며 시험관내 CBI 실험에서는 생후 50일군 유선조직의 microsome 분획의 발암원 활성화능이 보다 높음을 관찰하였다. 또한 T.C.D.D. 의존성 cytochrome P450 함량도 생후 50일군에서 가장 높았다. 그러나 불활화 효소들은 연령 변화에 따라 유의한 변화를 보여주지 않았다. 상기의 결과들은 DMBA나 NMU와 같은 발암물질이 특정조직, 특히 유선조직에 생후 50일군에서 유암을 선택적으로 유발하는 기전은 표적 조직의 높은 발암원 활성화능, 낮은 불활화등 그리고 효율이 낮은 DNA 수선능이 연계적으로 작동함으로써 이루어지고 있음을 보여주고 있다.

• 한국산업보건학회지
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• 제22권1호
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• pp.82-90
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• 2012

Objectives: This study was performed to provide workplaces with political guidelines that apply international CMRs (Carcinogens, Mutagens, Reproductive toxins) information to Public Notice of TLVs (Threshold Limit Values). We analyzed information supply status about CMRs of international agencies and compared substances for which TLVs are set in KMoEL (Ministry of Employment and Labor in Korea). Methods: We referred to the reliable literature about classification criteria of CMRs corresponding to UN GHS (Globally Harmonized System of classification and Labeling of chemicals) and Public Notice No. 2009-68 'Standard for Classification, Labeling of Chemical Substance and Material Safety Data Sheet' in KMoEL. The classification system of CMRs in professional organizations (IARC, NTP, ACGIH, EU ECHA, KMoEL, etc.) was investigated through the internet and literature. Conclusions: 191 chemical substances among total 650 substances with TLVs are classified as carcinogens. Also, 43 substances classified as mutagens, and 44 as reproductive toxicants. These results suggest that the information of CMRs in Public Notice of TLV will be reorganized to 191 carcinogens, 43 mutagens, and 44 reproductive toxicants.