• Title/Summary/Keyword: carcinogenic molecular

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Molecular Basis of Organospecific Carcinogensis by Chemical Carcinogens-Study with Breast Cancer Specific Carcinogens: DMBA as an Indirect-Acting carcinogen and NMU as a Direct-Acting cancinogen. (화학적 발암원의 조직 특이성 암유발기전 - DMBA와 NMU의 선택적 유암 발생기전을 중심으로 )

  • 박종영;김승원;박상철
    • Environmental Mutagens and Carcinogens
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    • v.9 no.1
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    • pp.1-12
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    • 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.

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The Influence of Land Use on the Concentration Levels and Distribution Characteristics of Polycyclic Aromatic Hydrocarbons (PAHs) in Korea (국내 토지이용도별 토양 중 다환방향족탄화수소류(PAHs)의 농도 수준 및 분포 특성)

  • Noh, Hoe-Jung;Yoon, Jeong Ki;Yun, Dae-Geun;Yu, Soon-Ju;Kim, Tae Seung;Lee, Jai-Young
    • Journal of Soil and Groundwater Environment
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    • v.19 no.6
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    • pp.59-71
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    • 2014
  • We investigated soil contamination depending on the land use by examining the contamination levels and distribution characteristics of 16 polycyclic aromatic hydrocarbons (PAHs) in the national soil. Total PAHs (the sum of 16 PAH concentrations) and carcinogenic PAHs (the sum of seven carcinogenic PAH concentrations) were $8.50{\sim}3,437.16{\mu}g/kg$ and $2.94{\sim}2,136.96{\mu}g/kg$, respectively. The concentration of benzo(a)pyrene, one of the contaminants regulated by the soil quality standard in the nation, was $ND{\sim}924.73{\mu}g/kg$. Its maximum value of $924.73{\mu}g/kg$ was detected in railroad (Region 3) and is approximately 13% of the standard value for Region 3 (i.e., 7 mg/kg). We also investigated the characteristics of contamination sources of PAHs in soil of the upland, forests, roads, and railroads, examining the fraction distribution of PAHs concentration by the number of benzene rings against the total PAHs concentration. The results demonstrate that the mean fraction of 4~6-ring PAHs against total PAHs concentration in soil was in the range of 51.8~80.7% with relative abundance of high-molecular PAHs, showing that the origin of contamination is under the category of combustion sources. When the molecular indices (Flu/(Flu/Pyr), Ant/(Ant+Phe), InP/(InP+BP), and BaA/(BaA+Chr)) were applied, they were also categorized as petroleum-based combustion sources. The individual PAH concentrations in soil by the land use were grouped into Regions 1, 2, and 3, which are statistically treated and are the parts of the national category system of soil quality standard. As a result, the concentration level of 16 PAHs was $0.02{\sim}2.63{\mu}g/kg$ in Region 1, $0.05{\sim}4.26{\mu}g/kg$ in Region 2, and $2.36{\sim}178.27{\mu}g/kg$ in Region 3. The concentration level of 6 carcinogenic PAHs was 14.2~320.4% against that of benzo(a)pyrene in Region 3 and sites of recycling waste sleepers. Considering that there were similarities among PAHs in terms of structures and toxicities, it would be recommended to review other types of carcinogenic PAHs together with benzo(a)pyrene when developing the soil quality standards in the nation.

Mechanism of guanine-specific DNA damage by UVA and its role in photocarcinogenesis and photoaging

  • Kawanishi, Shosuke;Oikawa, Shinji;Hiraku, Yusuke
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.150-153
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    • 2002
  • Solar UV light is a well-known carcinogen. UVA radiation is probably carcinogenic to humans. In addition, recent investigations point to the importance of UVA irradiation in the photoaging. We investigated the mechanism of sequence- specific DNA damage using $\^$32/P-Iabeled DNA fragments in relation to carcinogenesis and aging. Furthermore, we investigated whether UVA accelerates the telomere shortening in human WI-38 fibroblasts. The exposure of double- stranded DNA fragments to 365 nm light in the presence of endogenous sensitizers produced sequence-specific cleavage at the 5' site of 5'-GG-3' and 5'-GGG-3' sequences. In addition, HPLC analysis revealed that sensitizers plus 365 nm light increased the 8-oxodG content of double-stranded DNA. We discuss the mechanisms of guanine-specific DNA damagecaused by excited photosensitizers in relation to carcinogenesis and aging.

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Theoretical Studies on the Photo-Skinsensitizing Psoralens (I)

  • Ja-Hong Kim;Sang-Chul Shim
    • Bulletin of the Korean Chemical Society
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    • v.1 no.2
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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.

Primary Screening of QSAR Molecular Descriptors for Genotoxicity Prediction of Drinking Water Disinfection Byproducts (DBPs), Chlorinated Aliphatic Compounds

  • Kim, Jae-Hyoun;Jo, Jin-Nam;Jin, Byung-Suk;Lee, Dong-Soo;Kim, Ki-Tae;Om, Ae-Son
    • Environmental Mutagens and Carcinogens
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    • v.21 no.2
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    • pp.113-117
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    • 2001
  • The screening of various molecular descriptors for predicting carcinogenic, mutagenic and teratogenic activities of chlorinated aliphatic compounds as drinking water disinfection byproducts (DBPs) has been investigated for the application of quantitative structure-activity relationships (QSAR). The present work embodies the study of relationship between molecular descriptors and toxicity parameters of the genotoxicity endpoints for the screening of relevant molecular descriptors. The toxicity Indices for 29 compounds constituting the testing set were computed by the PASS program and active values were chosen. We investigate feasibility of screening descriptors and of their applications among different genotoxic endpoints. The correlation to teratogenicity of all 29 compounds was significantly improved when the same analysis was done with 20 alkanes only without alkene compounds. The HOMO (highest occupied molecular orbital) energy and number of Cl parameters were dominantly contributed.

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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.

Nested Multiplex PCR Based Detection of Human Papillomavirus in Cervical Carcinoma Patients of North- East India

  • Das, Debabrata;Rai, Avdhesh Kumar;Kataki, Amal Chandra;Barmon, Debabrata;Deka, Pankaj;Sharma, Jagannath Dev;Sarma, Anupam;Shrivastava, Sushruta;Bhattacharyya, Mouchumee;Kalita, Apurba Kumar;Sharma, Mousumi;Ahmed, Shiraj
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.785-790
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    • 2013
  • Background: Persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs), most commonly HPV types 16/18, has a significant role in cervical cancer initiation and progression. There are limited data available from north-east India about HPV prevalence though this region has high incidence rates of cervical cancer. The aim of this study was to investigate the HPV genotypes prevalent in cervical cancer patients of north-east India. Materials and Methods: We analyzed 107 cervical cancer patient samples. Nested multiplex PCR assays were employed for detection of 13 high risk and 5 low risk HPV types. Results: HPV was confirmed in 105 samples. The presence of 6 'carcinogenic' HPV types, HPV-16 (88%), -18 (15%), -31(4%),-45 (3%), -59 (4%), -58(1%), and one non carcinogenic, HPV-6/11 (6%), was recorded. Among various demographic and clinical factors only tumour stage showed a statistically significant association with HPV type infection (P=0.019). Conclusions: We suggest that the most prevalent genotype is HPV-16 followed by HPV-18 in cervical carcinoma patients of the north-eastern region of India. Advanced tumour stage may be associated with increased possibility of harbouring multiple HPV genotypes.

Simultaneous Determination of Alkoxyalcohols in Wet Wipes Using Static Headspace Gas Chromatography and Mass Spectrometry

  • Lee, Soojin;Pyo, Heesoo;Chung, Bong Chul;Kim, Haidong;Lee, Jeongae
    • Bulletin of the Korean Chemical Society
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    • v.35 no.11
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    • pp.3280-3288
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    • 2014
  • Alkoxyalcohols are used as solvents or preservatives in various consumer products such as wet wipes. The metabolites of alkoxyalcohols are known to be chronically toxic and carcinogenic to animals. Thus, an analytical method is needed to monitor alkoxyalcohols in wet wipes. The aim of this study was to develop a simultaneous analytical method for 14 alkoxyalcohols using headspace gas chromatography coupled with mass spectrometry to analyze the wet wipes. This method was developed by comparing with various headspace extraction parameters. The linear calibration curves were obtained for the method ($r^2$ > 0.995). The limit of detection of alkoxyalcohols ranged from 2 to $200ng\;mL^{-1}$. The precision of the determinative method was less than 18.20% coefficient of variation both intra and inter days. The accuracy of the method ranged from 82.86% to 119.83%. (2-Methoxymethylethoxy)propanol, 2-phenoxyethanol, and 1-phenoxy-2-propanol were mainly detected in wet wipes.

Decolorization of methyl red by selected bacteria in industrial waste sludge

  • Yim, Dae-Woo;Lee, Kang-Min
    • 한국생물공학회:학술대회논문집
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    • 2003.10a
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    • pp.398-401
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    • 2003
  • Azo dyes are aromatic compounds characterized by one or more azo bonds $(R_l-N=N-R_2)$. More than 800,000 tons of dyes are produced annually worldwide, of which 60-70% are azo dyes. During manufacturing, an estimated 10-15% is released into the environment. Aside from their negative aesthetic effects, certain azo dyes have been shown to be toxic and, in some cases, these compounds are carcinogenic and mutagenic. To establish biological wastewater treatment of azo dye, it is essential to discover azo dye-degrading microorganisms. In this report, sludge-contaminated with dyes were gathered through wastewater outlets from the industrial regions. The following to separation of bacteria within them, bacteria which decolorize methyl red, a azo dye, were selected and destined.

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Molecular Mechanisms of Regulation of Human Cytochrome P4501A2 Gene Expression

  • Chung, In-Jae
    • Natural Product Sciences
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    • v.10 no.5
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    • pp.197-206
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    • 2004
  • Cytochrome P4501A2 (CYP1A2) is responsible for the metabolic activation of a number of aromatic amines and amides to mutagenic and carcinogenic moieties. Considerable variations in the level of CYP1A2 expression in humans have been reported. Thus, the level of human CYP1A2 may determine an individuals susceptibility to these chemicals. Given its importance, the molecular mechanisms of CYP1A2 regulation have been studied by many groups. Direct interactions between transcription factors with the promoters of the gene represent one of the primary means by which the expression of CYP1A2 is controlled. In this review, several important cis elements, transcription factors and the effects of deacetylation/methylation of promoter regions that play an important role in the induction by PAHs as well as constitutive expression of human CYP1A2 are discussed.