• Title, Summary, Keyword: carcinogens

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Thresholds of Genotoxic and Non-Genotoxic Carcinogens

  • Nohmi, Takehiko
    • Toxicological Research
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    • v.34 no.4
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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.

Application of Molecular Orbital Theory to Biological chemistry (II). Interactions of Chemical Carcinogens with DNA Bases (分子軌道論의 生物化學에의 應用 (第 2 報). 發癌物質과 DNA 鹽基와의 相互作用)

  • Ho-Soon Kim;Yoon-Yul Park;Byung-Kak Park
    • Journal of the Korean Chemical Society
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    • v.24 no.4
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    • pp.280-287
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    • 1980
  • The interactions of chemical carcinogens, such as polycyclic aromatic hydrocarbons, dimethylaminoazobenzene (DAB) and its derivatives and heterocyclic compounds with tissue components, especially with deoxyribonucleic acid (DNA), were examined by means of simple Huckel method. Assuming that the formations of a loose molecular complex between the carcinogens and the tissue components are the first step of chemical carcinogenesis, the most proble orientation between the chemical carcinogens and adenine-thymine (A=T) pair or guanine-cytosine $(G\equivC)$ pair is determined. It has been found that, in the case of the formation of molecular complex between chemical carcinogens and A=T pair, the two atoms of K-region of the carcinogens and the atom of L-region in the proximity of their K-region are combined correspondingly with C-l' carbon atom in the sugar that is attached to thymine, N-1 nitrogen atom and C-5 carbon atom in the thymine part of A=T pair, while, in the case of that between the carcinogens and $G\equivC$ pair, the above three atoms of the carcinogens are combined correspondingly with C-8 carbon atom, N-9 nitrogen atom and N-3 nitrogen atom in the guanine part of $G\equivC$ pair.

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Effect of Chemical Carcinogens on the Replication, Cytolyticity, DNA Synthesis, and Protein Expression of Herpes Simplex Virus in Viral Infected Cells (발암성 화학물질들이 Herpes Simplex Virus의 복제, 세포융해, DNA 합성 및 단백질 합성에 미치는 효과)

  • Chun, Yeon-Sook
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.213-222
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    • 1992
  • We investigated effects of several chemical carcinogens, i.e., $benzo({\alpha})pyrene$ (BP),7,12-dimethylbenz(a)anthracene (DMBA), nitrosomethyl urea (NMU), and nicotine on the replication, cytolyticity, DNA synthesis, and protein synthesis of type 1 herpes simplex virus (HSV-1) in viral infected Vero cell monolayers. We observed that the BP and DMBA did not show such activity. All chemical carcinogens did not inhibit the synthesis of viral DNA, but the expression of gamma viral proteins that are expressed from the newly synthesized progeny viral DNA was somewhat notably inhibited by BP and DMBA. However, the synthesis of alpha and beta viral proteins was not altered by the chemical carcinogens. These data indicate that the gamma viral proteins expressed from the newly synthesized DNA in the presence of chemical carcinogens in the culture medium may be defective. This is further supported by the fact that the virus fail to replicate in the presence of these chemical carcinogens, in spite of viral DNA and proteins are somewhat normally synthesized.

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Effect of Genotoxicity or Carcinogenecity Chemicals on the ROS Production (유전독성, 발암성 화학물질이 ROS 생성에 미치는 영향)

  • Go, Seo-Youn;Sheen, Yhun-Yhong
    • Environmental health and toxicology
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    • v.23 no.1
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    • pp.23-32
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    • 2008
  • In the present study, ROS detection of L5178Y cells that were treated with twenty test compounds in order to find out hydrogen peroxide ($H_2O_2$) induction for genotoxicity and carcinogenic toxicity. Twenty test compounds were consist of four classes, such as genotoxic carcinogens, genotoxic noncarcinogens, nongenotoxic carcinogens, and nongenotoxic noncarcinogens. Genotoxic carcinogens are 1,2-dibromoethane, glycidol, melphalan, diethylstilbestrol and urethane. Genotoxic noncarcinogens are 8-hydroxyquinoline, emodin, acetonitrile and diallylphthalate, L-ascorbic acid. Nongenotoxic carcinogens are methyl carbamate, O-nitrotoluene, 1,4-dioxane, tetrachloroethylene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. And nongenotoxic noncarcinogens are D-mannitol, 1,2-dichlorobenzene, caprolactam, bisphenol A and chlorpheniramine maleate.

QSAR Approach for Toxicity Prediction of Chemicals Used in Electronics Industries (전자산업에서 사용하는 화학물질의 독성예측을 위한 QSAR 접근법)

  • Kim, Jiyoung;Choi, Kwangmin;Kim, Kwansick;Kim, Dongil
    • Journal of Environmental Health Sciences
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    • v.40 no.2
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    • pp.105-113
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    • 2014
  • Objectives: It is necessary to apply quantitative structure activity relationship (QSAR) for the various chemicals with insufficient toxicity data that are used in the workplace, based on the precautionary principle. This study aims to find application plan of QSAR software tool for predicting health hazards such as genetic toxicity, and carcinogenicity for some chemicals used in the electronics industries. Methods: Toxicity prediction of 21 chemicals such as 5-aminotetrazole, ethyl lactate, digallium trioxide, etc. used in electronics industries was assessed by Toxicity Prediction by Komputer Assisted Technology (TOPKAT). In order to identify the suitability and reliability of carcinogenicity prediction, 25 chemicals such as 4-aminobiphenyl, ethylene oxide, etc. which are classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC) were selected. Results: Among 21 chemicals, we obtained prediction results for 5 carcinogens, 8 non-carcinogens and 8 unpredictability chemicals. On the other hand, the carcinogenic potential of 5 carcinogens was found to be low by relevant research testing data and Oncologic TM tool. Seven of the 25 carcinogens (IARC Group 1) were wrongly predicted as non-carcinogens (false negative rate: 36.8%). We confirmed that the prediction error could be improved by combining genetic toxicity information such as mutagenicity. Conclusions: Some compounds, including inorganic chemicals and polymers, were still limited for applying toxicity prediction program. Carcinogenicity prediction may be further improved by conducting cross-validation of various toxicity prediction programs, or application of the theoretical molecular descriptors.

Review for CAREX(CARcinogen EXposure) Exposure Surveillance System: Limitation and Application to Korea (발암인자 노출감시를 위한 CAREX(CARcinogen EXposure, CAREX) 프로그램 고찰; 한계점과 활용 방안)

  • Jung, Hyejung;Ryu, Seunghun;Jang, Jiyoung;Kim, Seungwon;Ha, Kwonchul;Koh, Donghee;Kim, Won;Bae, Hyunjoo;Yoon, Chungsik;Yi, Kyonghui;Yi, Gwangyong;Kwak, Hyunseok;Shin, Jungah;Park, Donguk
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.24 no.3
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    • pp.247-255
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    • 2014
  • Objectives: We reviewed the CAREX (CARcinogen EXposure) program designed to estimate the prevalence of occupational exposure to carcinogens and summarized the advantages and limitations of this program. Methods: All literature, including reports on CAREX and the use of CAREX, were reviewed. The keyword search term was CAREX. Additional articles were identified from references cited in articles and reviewed. Results: An exposure information system, CAREX was developed based on data from the Finnish Institute of Occupational Health of Finland and from the US. CAREX has been applied in several countries, including in the EU, in order to estimate national exposure patterns to carcinogens. The initial exposure assessment carried out through CAREX was aimed at estimating exposures over the period of 1990-1993. To estimate the number of workers exposed to carcinogens by using CAREX, reference exposure prevalence from Finland and the United States was computed, which was then reviewed and corrected by national experts. Finally the overall number of workers exposed to carcinogens can be estimated. We found that CAREX has been used in a total of 18 countries. No Asian country has used CAREX. Conclusions: CAREX can be applied not only to estimate the number of workers exposed to carcinogens in Korea, but also to identify high-risk industries with workers most exposed to carcinogens.

Suggestion for the Prevention of Occupational Cancer in Korea (한국에서의 직업성 암 예방을 위한 제언)

  • Kim, Won;Kim, Shin-Bum;Choi, In-Ja;Kwag, Hyun-Seok
    • Journal of Environmental Health Sciences
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    • v.36 no.6
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    • pp.518-526
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    • 2010
  • There are millions of deaths from cancer worldwide every year. Among them, 4~10% are considered to be attributable to occupational factors and 0.6 million workers die annually from work-related cancers. Occupational cancers are relatively preventable compared with the cancers associated with other factors. In the developed countries, especially in Europe, there have been hundreds of occupational cancers reported annually in the respective nation-states. However, there were only 35 cases reported in Korea in the 1990s which were accepted as being work-related cancers. This difference might be related to a low level of recognition, detection, and acceptance of occupational cancer and carcinogens in Korea. To prevent the risk of exposure to carcinogens a comprehensive list of carcinogens must be prepared. This should be followed by timely dissemination of information which will enable fundamental controls to be implemented, such as the imposition of ban, substitution, and engineering controls. This will require setting up procedures to record the past use and exposure data and carrying out robust statistical analyses of that data on occupational cancers and carcinogens.

Critical Review on Carcinogenicity of Metalworking Fluids (절삭유(Metalworking Fluids)의 발암성에 대한 고찰)

  • 박동욱;윤충식;이송권
    • Journal of the Korean Society for Precision Engineering
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    • v.20 no.1
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    • pp.50-62
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    • 2003
  • Exposure to metalworking fluids (MWFs) has significantly been associated with cancer developed in multi-organs, respiratory diseases and skin diseases. Several carcinogens to humans or animals are contained in MWFs. They have been reported to be mineral oils, polynuclear aromatic hydrocarbons (PAHs), formaldehyde and N-nitrosodiethanolamine (NDELA). The great hazards of MWF have forced the advanced country including United States to regulate carcinogens contained in MWF. In 2001, American Conference of Governmental Industrial Hygienists (ACGIHs) regarded MWF mist as suspected carcinogen to human (A2) and added it to “Notice of Intended Change (NIC)” list of 2001. In spite of the fact that much MWF has widely been used in many industries using machines, Korea has no legal actions for management of MWF. What is worse, even toxicity such as Carcinogenicity has not been reported. KS (Korean Standards) lists 7 advices of MWF but it does net state the hazards to health. It is very hard to control or minimize worker's exposure to MWF containing many carcinogens. Prier to the introduction of MWF to workplace, it is the most effective measure to regulate carcinogens below a certain level. Regulation on the content of PAH seems to be necessary because less amount of PAH in mineral oils improves the quality of MWF. Also, addition of nitrosating groups to MWF should be prohibited to minimize worker's exposure to NDELA. Employers and manufacturers should indicate the Carcinogenicity of all carcinogens in MWFs in Material Safety Data Sheets (MSDS) in order fer workers to recognize Carcinogenicity. Legal actions have to be taken to protect workers from health hazards due to exposure to MWF by further investigation on MWF.

A study on the criteria and supply status of information for managing carcinogens in domestic and foreign (국내외 발암성물질의 관리기준과 정보제공 현황에 관한 연구)

  • Lee, Kwon Seob;Lee, Jong Han;Lee, Hye Jin
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.21 no.1
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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.

Finding of a Characteristic Reactive Region Common to Some Series of Chemical Carcinogens

  • Park, Byung-Kak;Lee, Moon-Hawn;Do, Sung-Tag
    • Bulletin of the Korean Chemical Society
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    • v.6 no.2
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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.

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