• Title, Summary, Keyword: carcinogenic molecular

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Photochemical and Thermal Reaction Mechanism for the Reaction of Carcinogenic Molecules and Food Reservatives (발암성 분자와 식품보존제의 광화학 및 열적 반응메카니즘)

  • 김민식;채기수;김갑순;성대동
    • The Korean Journal of Food And Nutrition
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    • v.11 no.3
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    • pp.267-271
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    • 1998
  • The photochemical carcinogenic reaction mechanism and molecular carcinogenic intensity through the reaction of dibromo carbene and diazomethane with dehydroacetic acid and coumarin have been studied under the two kinds of photolysis. The reaction intensities show the degree of carcinogenic activity. Under the condition of UV/vis light source, the yield of high toxic carcinogenetic carbene intermediate is produced less than those of the laser flash photolysis.

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Quantitative Approaches to Assess Key Carcinogenic Events of Genotoxic Carcinogens

  • Fukushima, Shoji;Gi, Min;Fujioka, Masaki;Kakehashi, Anna;Wanibuchi, Hideki;Matsumoto, Michiharu
    • Toxicological Research
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    • v.34 no.4
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    • pp.291-296
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    • 2018
  • Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts ${\ll}$ Mutations ${\ll}$ GST-positive foci (preneoplasia) ${\ll}$ Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.

The Theoretical Studies for the (Molecular Connectivity법에 의하여 발암성 Benzenoid 탄화수소의)

  • Ui Rak Kim;Jong Guk Eun;Myung-Jae Lee;Kim Sang Hae
    • Journal of the Korean Chemical Society
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    • v.31 no.2
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    • pp.153-161
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    • 1987
  • The carcinogenicity of benzenoid hydrocarbons apparently depends strongly on the topological nature of the molecule. The existance of certain regions in the structure which are known propensity of benzenoid hydrocarbons to be carcinogenic. We try to identify the correlation between the number of potentially carcinogenic bay region in each of them and the quantity of Molecular Connectivity Index for 81 benzenoid hydrocarbons. Results indicate an excellent linear correlation between the number of bay region and the quantity of molecular connectivity index except the molecular containing single bond in their structure.

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Carcinogenic Role of Tumor Necrosis Factor-α Inducing Protein of Helicobacter pylori in Human Stomach

  • Suganuma, Masami;Kuzuhara, Takashi;Yamaguchi, Kensei;Fujiki, Hirota
    • BMB Reports
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    • v.39 no.1
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    • pp.1-8
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    • 2006
  • Helicobacter pylori is the definitive carcinogen for stomach cancer and is known to induce proinflammatory cytokines, such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1(IL-1) in the stomach. Based on our findings that TNF-$\alpha$ is an endogenous tumor promoter, we identified the TNF-$\alpha$ inducing protein (Tip$\alpha$) gene family, and confirmed Tip$\alpha$ and HP-MP1 as new carcinogenic proteins of H. pylori. Tip$\alpha$ protein is unique to H. pylori, and this paper shows the strong tumor promoting activity of Tip$\alpha$ gene family, in cooperation with Ras protein and its mechanisms of action in relation to NF-${\kappa}B$ activation, and discusses the carcinogenic role of Tip$\alpha$ in stomach cancer. Our recent finding showing that penicillin-binding proteins of other bacteria are weak homologues of Tip$\alpha$ is also discussed.

Quantitative and Qualitative Extrapolation of Carcinogenesis Between Species

  • Gold Lois Swirsky;Manley Neela B.;Ames Bruce N.
    • 대한예방의학회:학술대회논문집
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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 Carcinogenic Region of Benzo[a]pyrene Metabolites and Its Molecular Complex with Guanine and Adenine (Benzo[a]pyrene 대사체의 발암활성 영역 및 DNA 염기와의 분자착물의 배향)

  • Kim, Jong Moon;Son, Gwan Su;Doh, Seong Tak;Kim, Seog Kyu;Park, Byung Kak
    • Journal of the Korean Chemical Society
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    • v.40 no.4
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    • pp.229-234
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    • 1996
  • Carcinogenicities of Benzo[a]pyrene(BP) and its metabolites were investigated by PM3. The 4, 5, 5a, and 6 positions forming transbutadiene(TB) frame in BP have been proved to be carcinogenic region by LUMO. We have found that the carcinogenic region of BP-triol, ultimate cacinogen, is shifted from 4, 5, 5a, and 6 positions of precarcinogen to 10, 10a, 12c, and 12b ones. The appreximate charge transfer quantities turned out to have the largest value between HOMO of Guanine and LUMO of BP-triol corresponding to TB region on each other.

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Novel Genotoxic Strategies for Efficiently Detect Chemicals' Carcinogenicity (노동자 건강보호를 위한 최신 유전독성학 연구전략)

  • Rim, Kyung-Taek
    • Journal of Environmental Health Sciences
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    • v.44 no.1
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    • pp.31-43
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    • 2018
  • Objectives: Effective genetic toxicology and molecular biology research techniques and strategies that are highly correlated with the carcinogenic inhalation toxicity test and related research are required. The aim of this study was to maximize the utilization of chemical substances to prevent workers' occupational diseases. Methods: We surveyed the literature, domestic and international references, and the status of relevant domestic and foreign professional organizations. Expert advisory opinions were reflected, and experts were consulted by participating in domestic and overseas academic conferences. Results: The current status of domestic and international genotoxic toxicity evaluation was examined through various documents from related organizations. Cell models for in vitro lung toxicology were investigated and summarized, and the human resources and performance results of genetic toxicity studies and pilot projects were compared and analyzed by holding an advisory meeting. We examined domestic and international genotoxicity guidelines and investigated new test methods for the development of genotoxicity and carcinogenicity. Ultimately, we described long-term future predictions, including the implementation of our researchers' recommendations and occupational genetic toxicology forecasts for future worker health protection. Conclusions: This research project aims to establish current genetic toxicology and molecular biology research techniques and strategies that can maximize the linkage with the carcinogenic inhalation toxicity test and research in the future. We expanded the study of genetic toxicity and establish a foundation forgenetic toxicity in accordance with research trends in Korea and abroad.

Curcumin: a Polyphenol with Molecular Targets for Cancer Control

  • Qadir, Muhammad Imran;Naqvi, Syeda Tahira Qousain;Muhammad, Syed Aun
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2735-2739
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    • 2016
  • Curcumin, is a polyphenol from Curcuma longa (turmeric plant), is a polyphenol that belongs to the ginger family which has long been used in Ayurveda medicines to treat various diseases such as asthma, anorexia, coughing, hepatic diseases, diabetes, heart diseases, wound healing and Alzheimer's. Various studies have shown that curcumin has anti-infectious, anti-inflammatory, anti-oxidant, hepatoprotective, thrombosuppressive, cardio protective, anti-arthritic, chemo preventive and anti-carcinogenic activities. It may suppress both initiation and progression stages of cancer. Anticancer activity of curcumin is due to negative regulation of inflammatory cytokines, transcription factors, protein kinases, reactive oxygen species (ROS) and oncogenes. This review focuses on the different targets of curcumin to treat cancer.

Epigenetic Field for Cancerization

  • Ushijima, Toshikazu
    • BMB Reports
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    • v.40 no.2
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    • pp.142-150
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    • 2007
  • Epigenetic alterations, represented by aberrant DNA methylation, are deeply involved in human cancers. In gastric cancers, tumor-suppressor genes are inactivated more frequently by promoter methylation than by mutations. We recently showed that H. pylori infection, a potent gastric carcinogenic factor, induces methylation of specific genes in the gastric mucosae. When the methylation levels were analyzed in the gastric mucosae of healthy volunteers, cases with a single gastric cancer, and cases with multiple gastric cancers, who have increasing levels of risks for gastric cancers, there was a significant increasing trend in the methylation levels among the individuals without current H. pylori infection. This finding unequivocally showed the presence of an epigenetic field for cancerization. The degree of the field defect was measured more conveniently using methylation levels of marker genes than using those of tumor-suppressor genes. The presence of an epigenetic field for cancerization has been indicated for liver, colon, Barrett's esophageal, lung, breast, and renal cancers. Since decreased transcription is involved in the specificity of methylated genes, it is likely that specific genes are methylated according to carcinogenic factors. These findings emphasize the usefulness of DNA methylation as a marker for past exposure to carcinogens and future risk of cancer development.

Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity

  • Shimada, Tsutomu
    • Toxicological Research
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    • v.33 no.2
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    • pp.79-96
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    • 2017
  • A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), aryl- and heterocyclic amines and tobacco related nitrosamines, are ubiquitous environmental carcinogens and are required to be activated to chemically reactive metabolites by xenobiotic-metabolizing enzymes, including cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of various human P450 enzymes determined to date, CYP1A1, 1A2, 1B1, 2A13, 2A6, 2E1, and 3A4 are reported to play critical roles in the bioactivation of these carcinogenic chemicals. In vivo studies have shown that disruption of Cyp1b1 and Cyp2a5 genes in mice resulted in suppression of tumor formation caused by 7,12-dimethylbenz[a]anthracene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, respectively. In addition, specific inhibitors for CYP1 and 2A enzymes are able to suppress tumor formation caused by several carcinogens in experimental animals in vivo, when these inhibitors are applied before or just after the administration of carcinogens. In this review, we describe recent progress, including our own studies done during past decade, on the nature of inhibitors of human CYP1 and CYP2A enzymes that have been shown to activate carcinogenic PAHs and tobacco-related nitrosamines, respectively, in humans. The inhibitors considered here include a variety of carcinogenic and/or non-carcinogenic PAHs and acethylenic PAHs, many flavonoid derivatives, derivatives of naphthalene, phenanthrene, biphenyl, and pyrene and chemopreventive organoselenium compounds, such as benzyl selenocyanate and benzyl selenocyanate; o-XSC, 1,2-, 1,3-, and 1,4-phenylenebis(methylene)selenocyanate.