• Journal of the Korean Chemical Society
• /
• v.24 no.4
• /
• pp.280-287
• /
• 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.

• The Korean Journal of Pharmacology
• /
• v.28 no.2
• /
• pp.213-222
• /
• 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.

• Toxicological Research
• /
• v.34 no.4
• /
• pp.281-290
• /
• 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
• /
• v.6 no.2
• /
• pp.103-107
• /
• 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
• /
• v.28 no.6
• /
• pp.504-508
• /
• 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
• /
• v.8 no.2
• /
• pp.317-329
• /
• 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
• /
• v.17 no.3
• /
• pp.151-167
• /
• 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.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.21 no.1
• /
• pp.40-48
• /
• 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.

• Environmental Mutagens and Carcinogens
• /
• v.9 no.1
• /
• pp.1-12
• /
• 1989

To study the selective organospecific carcinogenesis by the specific chemical carcinogens, the breast cancer induction model by oral administration of 7, 12-dimethylbenzanthracene (DMBA) or by intravenous injection of N-methylni-trosourea (NMU) on female rats was analyzed. In the present experiment, we compared the effexts of ages on the chemical mammary carcinogenesis by studying the metabolic system of the carcinogenic activation, detoxification or DNA damage and repair. The breast tumor incidence was significantly higher in the young rats of 50 days old than in those of one year old rats. As an index of organospecific DNA damage or repair, the in vivo covalent binding index(CBI) of the specific organs by the specific chemical carcinogens was monitored. And for the analysis of carcinogenic activation, the quantity of cytochrome P450`s was determined with the respective type-specific monoclonal antibody, while the detoxication capacity was deduced by the activity monitoring of glutathione S-transferase (GST) and peroxidase. The skin tissues of the mammary region had the highest CBI with both of DMBA and NMU at 50 days of age. And there were contrasting differences in the contents of carcinogenic activation and detoxication system: that is, the content of T.C.D.D.-inducible cytochrome P450 was high, while the activities of GST and peroxidase was low in the mammary skin tissues at tumor prevalent age. These results led us to conclude that the molecular organospecific carcinogenesis, as illustrated with mammary carcinoge-nesis by DMBA and NMU, is operated probably through the differential capacity of the target tissues in the high carcinogenic activation, low detoxication and the low DNA repair function.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.22 no.1
• /
• pp.82-90
• /
• 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.