• Title/Summary/Keyword: chemical direct mutagens

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Screening of Mutagenicity and Antimutagenic Activity against Chemical Direct Mutagens of Ethanolic Extracts from Colored Rice Bran (유색미 에탄올 추출물의 변이원성 및 화학적 직접변이원에 대한 항변이원 활성 검정)

  • Nam, Seok-Hyun;Chang, Su-Min;Kang, Mi-Young
    • Applied Biological Chemistry
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    • v.45 no.4
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    • pp.195-202
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    • 2002
  • The cytotoxic, mutagenic and antimutagenic activities against chemical direct mutagens such as mitomycin C, 4-nitroquinoline-N-oxide, 2,4,7-trinitro-9-fluorenone of the 70% ethanol extracts of 29 colored rice varieties and chuchung as a control were examined. The results obtained using authentic alkaline phosphatase activity as a growth representative of the indicator cell E. coli PQ 37 demonstrated that the extracts of 13 kinds of colored rice varieties including Jumlalocal and Jumlalocal-1 showed strong toxic effect on the cell growth. However the extracts of DK 1, SC-5, LK 1A-2-12-1-1 and wx 139-3-64-20-3-1 seemed to have stimulatory effects on the cell growth. The mutagenicity and antimutagenicity of the colored rice varieties were screened using SOS chromotest. The mutagenic activity was detected from Jumalocal-1, IR 17491-5-4-3-3 and Jumlalocal. On the contrary, 7 samples including LK 1-3-6-12-1-1, Parnkhari 203, Jumlalocal, wx 139-3-64-20-3-1, Muthumanikam, HP 883-1-1-1-B-1-1 and Jumlalocal-1 were shown to have antimutagenic acitivities against the chemical direct mutagens used in this study.

N-nitroso-N-methylurea and N-nitroso-N-ethylurea Decrease in Nitric Oxide Production in Human Malignant Keratinocytes

  • Moon, Ki-Young
    • Biomedical Science Letters
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    • v.24 no.1
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    • pp.50-54
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    • 2018
  • N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), direct alkylating chemical mutagens and carcinogens, are shown to be the upregulators of cellular $NF-{\kappa}B$, regulating various genes that mediate tumorigenesis and carcinogenesis. Nitric oxide (NO), a toxic reactive radical gas, has been known to induce programmed cell death or apoptosis in various cells. Therefore, the assessment of NO production was examined to elucidate the possible contribution of NO release to the chemical carcinogenic potency of NMU and NEU in human skin cells. NMU and NEU did not alter the NO production, but they caused a significant downregulation of the NO generation on lipopolysaccharide (LPS)-induced NO production at concentrations ranging from $2{\sim}5{\mu}M$. The degree of downregulation of NO by NMU and NEU decreased up to 15% and 20%, respectively, compared to the control. These results demonstrate that the LPS-inducible keratinocytes NO synthase is involved in modulating carcinogenic potency by NMU and NEU, and the regulation of the cellular $NF-{\kappa}B$ activity by NMU and NEU is negatively correlated with the level of LPS-induced NO production in human skin cells. The findings of this study suggest the hypothesis that NMU and NEU-induced carcinogenesis may be associated with the downregulation of NO production, and the inducible NO may play an important role in NMU and NEU-induced carcinogenicity in human epidermal keratinocytes.

Chemical Characteristics and Mutagenicities of Carcinogenic Extractable Organic Matters in Airborne Particulates (대기 부유분진중 발암성 유기추출물의 화학적 조성 및 돌연변이원성)

  • Chung, Yong;Shin, Dong-Chun;Park, Seong-Eun;Hwang, Man-Sik;Lee, Hyun
    • Environmental Mutagens and Carcinogens
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    • v.15 no.2
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    • pp.131-139
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    • 1995
  • Air suspedned particulates are the most serious factor among air pollutants in Seoul and their extracts have been revealed to be pulmonary carcinogenes. Air particulates were collected at a site representative of the high traffic area of Seoul from December 1993 to May 1994. Polycyclic aromatic hydrocarbons (PAHs) and nitroarenes in organic extracts of air particulates were determined by gas chromatography and mutagenicity of particle extracts was evaluated by the pre-incubation procedure with Salmonella typhirnurium TA98 and TA 98NR. The average concentration of total suspended particulates and inhalable (less than 10 $\mu$m) particulates were 169.63 $\mu g/m^3$, 141.92 $\mu g/m^3$, respectively. The relative contribution of organic matters was highest in neutral fraction and was lowest in basic fraction. Among identified 20 PAHs, the level of PAHs with 4-benzen ring i.e., pyrene, benzo(a)anthracene and chrysene were much higher than the PAHs with higher ring numbers. The mutagenicity of air particulates was much higher in the presence of rat liver microsomai fraction (S9 mixture) than that observed in its absence, which indicates that air particulates contained both direct and indirect mutagens. Nitroarenes in this study were not almost detected but mutagenicity of their fraction was higher. These results are represent to research for the identification of nitroarenes in the forward study.

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Micronucleus Test for the Classification of Chemical Mutagenicity according to Globally Harmonized System

  • Rim, Kyung-Taek;Kim, Hyeon-Yeong;Chung, Yong-Hyun
    • Journal of Applied Biological Chemistry
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    • v.56 no.4
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    • pp.191-197
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    • 2013
  • To classify the chemical hazard according to globally harmonized system of classification and labeling of chemicals (GHS), we investigated the genotoxicity of three chemicals, methyl myristate, 2-ethylhexanoic acid zinc salt, N,N,N',N'-tetrakis(2-hydroxyethyl) ethylenediamine, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these three chemicals have already been tested numerous times, a micronucleus test has not been conducted. The seven week-old male ICR mice were tested at three dosages for the three chemicals, respectively. After 24 h of oral administration with the three chemicals, the mice were sacrificed and their bone marrow cells were prepared for smearing slides. As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes, all treated groups expressed no statistically significant increase of MNPCE compared to the negative control group. There were no clinical signs related with the oral exposure of these three chemicals. It was concluded that these three chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and there was no direct proportion with dosage. These results indicate that the three chemicals have no mutagenic potential under each test condition, and it is not classified these chemicals as mutagens by GHS.

Mutagenicity and Antimutagenicity of Hydrophilic and Lipophilic Extracts of Thai Northern Purple Rice

  • Punvittayagul, Charatda;Sringarm, Korawan;Chaiyasut, Chaiyawat;Wongpoomchai, Rawiwan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9517-9522
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    • 2014
  • Purple rice (Oryza sativa L. var. indica) cv. Kum Doisaket is cultivated in northern Thailand. This study evaluated the mutagenic and antimutagenic properties of hydrophilic and lipophilic components of purple rice using the Ames test. The seed and hull of purple rice were extracted with hexane, methanol, ethanol, and water. The methanol extracts had the highest amounts of phenolic acids and flavonoids, while the hexane extracts contained large amount of tocols and ${\gamma}$-oryzanol. None of the extracts were mutagenic in Salmonella typhimurium strains TA98 and TA100. The hexane extract of rice hull and the methanol extract of rice seed were strongly effective against aflatoxin B1- and 2-amino-3, 4 dimethylimidazo (4, 5-f) quinoline-induced mutagenesis, while aqueous extracts showed weakly antimutagenic properties. All extracts with the exception of aqueous extracts enhanced the number of revertant colonies from benzo (a) pyrene induced-mutagenesis. None of the extracts inhibited mutagenesis induced by the direct mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide and sodium azide. The hull extracts showed more potent antimutagenicity than the seed extracts. Based on a chemical analysis, ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol in the hull and cyanidin-3-glucoside and peonidin-3-glucoside in the seed are candidate antimutagens in purple rice. The antimutagenic mechanisms of purple rice might be related to either modulation of mutagen metabolizing enzymes or direct attack on electrophiles. These findings supported the use of Thai purple rice as a cancer chemopreventive agent.

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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