• Title/Summary/Keyword: direct mutagen

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EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON CYTOCHROME P-450-DEPENDENT DRUG METABOLISM IN PRIMARY MOUSE HEPATOCYTES CULTURES AND MOUSE HEPATOMA CELLS

  • Jung, Hyun-Ho;Jeong, Hye-Gwang;Lee, Michael
    • Toxicological Research
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    • v.9 no.2
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    • pp.177-186
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    • 1993
  • Previous results from several laboratories have demonstrated that tumor necrosis factor-alpha (TNFalpha) depressed cytochrome P-450 (P-450)-dependent drug metabolism in vivo. However, there is some debate whether the action of TNFalpha is mediated by its direct effects on hepatocytes, or is indirectly mediated through the release of other mediators like IL-1 from macrophages. In the present studies, we investigated the effects of TNFalpha on P-450-dependent drug metabolizing enzyme as measured by 7-ethoxyresorufin O-deethylase (EROD) activity.

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IN VITRO IMMUNOTOXICITY OF MBP, A MAJOR METABOLITE OF DI-N-BUTYL PHTHALATE(DBP) ON SD RAT SPLENIC B CELLS AND HUMAN B LYMPHOMA CELLS

  • Juno H. Eom;Chung, Seung-Tae;Park, Jae-Hyun;Lee, Jong-Kwon;Oh, Hae-Young;Kim, Hyung-Soo
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.186-186
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    • 2002
  • Di-n-butyl phthalate(DBP) is one of the most commonly used phthalic acid esters(PAEs) as a plasticizer, a solvent or a component in cosmetic formulations. MBP(monobutyl phthalate) is a major metabolite of DBP. Although DBP has been identified as a reproductive toxicant in several animal species and also known as a endocrine disruptor, the direct or indirect immunomodulatory effect of DBP has been little reported.(omitted)

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Inhibitory Effect of Main Pine Needle Extracts on the Chemically Induced Mutagenicity (주요 솔잎 추출물의 돌연변이 억제효과)

  • Kim, Eun-Jeong;Jung, Sung-Won;Choi, Keun-Pyo;Ham, Seung-Shi;Kang, Ha-Young
    • Korean Journal of Food Science and Technology
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    • v.30 no.2
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    • pp.450-455
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    • 1998
  • Pine has been known as a traditional medicinal plant and as showing a physically beneficial function to a human being. Therefore, this study was performed to investigate the physiological activities of main pine neddles. Ethanol extracts from pinus needles did net exhibit any mutagenicity. On the contrary, inhibitory effects of ethanol extract were observed on mutagenicity induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), 4-nitroquinoline-1-oxide (4NQO), 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1) and benzo(a)pyrene $(B({\alpha})P)$ using Salmonella typhimurium reversion assay. On direct-acting mutagen (MNNG, 4NQO) and indirect-acting mutagen (Trp-P-1, $(B({\alpha})P)$, we observed higher inhibitory effect. Stepwise fractionation of the ethanol extract was done by using ether, chloroform, ethyl acetate, butanol and water to obtain effective fraction. Among them, water fractions $(100\;{\mu}g/plate)$ of Pinus thunbergii, Pinus rigida, Pinus densiflora and Pinus koraiensis showed high inhibition of 91.65%, 94.7%, 84.22% and 79.02%, respectively, on the mutagenicity of MNNG in Salmonella typhimurium TA100.

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Effect of Mugwort Extract on the in vitro Mutagenicity, Desmutagenicity. (쑥 추춤물의 항돌연변이 활성효과)

  • Lee, Sung;Kwon, Dong-Jin;Yoo, Jin-Young;Chung, Dong-Hyo
    • Microbiology and Biotechnology Letters
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    • v.24 no.1
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    • pp.105-110
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    • 1996
  • Mugwort has been known as a traditional substitutive foodstuff and as showing a physiologically beneficial function to a human being. Therefore, effect of mugwort extract in terms of mutagenicity and desmutagenicity was investigated to berify its function. Ethanol extract from mugwort did not exhibit any mutagenicity. On the contrary, inhibitory effects of the ethanol extract were observed on mutagenicity induced by aflatoxin $B_{1}(AFB_1)$, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole(Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole(Trp-P-2) and 2-nitroflourene(2NF) using Salmonella typhimurium reversion assay. On direct-acting mutagen(2NF, 3${\mu}$g/plate), ethanol extract showed a slight inhibitory effect of 19.7~22.9%, however on indirect-acting mutagen such as AFB1(2${\mu}$g/plate), Trp-P-1(1${\mu}$g/plate) and Trp-P-2(1${\mu}$g/plate), we observed higher inhibitory effect of 47.9~61.2%, 64.1~70.7%, 67.4~78.7%, respectively. Step-wise fractionation of the ethanol extract was done by using hexane, chloroform, ethyl acetate and water to obtain effective fraction. Among them, hexane, chloroform, and ethyl acetate fractions showed high inhibition of 63.0~80.0%, 77.5~82.1%, and 68.5~83.1%, respectively on the mutagenicity of $AFB_1$ in Sal. typhimurium TA98. Consequently, these results indicated that mugwort extract contains some compound(s) which may show desmutagenicity.

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Increased Preservative and Antimutagenic Activities of Kimchi with Addition of Green Tea Leaves

  • Park, Woon-Young;Park, Kun-Young
    • Preventive Nutrition and Food Science
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    • v.5 no.4
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    • pp.189-193
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    • 2000
  • Preservative and antimutagenic effects of green tea leaves added Chinese cabbage kimchi (GK1, GK2, GK3, and GK4 : 1, 2, 3 and 4 of green tea leaves (GTL) in proportion of 100 of salted Chinese cabbage were added to kimchi) were compared to those of the Chinese cabbage kimchi without GTL (control kimchi, CK). Fermentation period of GKs was further delayed than that of CK. The initial pH and acidity between GKs an CK were similar, but the time reach optimally ripened status of kimchi (pH 4.3) was different. CK took 6 days, while GK1, GK2, GK3 and GK4 took 6, 10, 12 and 14 days at 10℃, respectively. The growth of Leuconostoc sp. and Lactobacilus sp. in GKs delayed comparing to those in FCK. Among GKs, as the added amount of green tea leaves increased, the growth of lactic acid bacteria was retarded. The antimutagenic effects of juices from GKs and CK were studied against aflatoxin B₁(AFB₁) in the Ames test on Salmonella typehimurium TA100 and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the SOS chromotest using E. coli PQ37. Juices from optimally ripened GKs (pH 4.3) showed 52∼76% inhibition rates against the indirect mutagen, aflatoxin B₁ induced mutagenicity while 49% inhibition rate by CK in the Ames test. Juices from GKs and CK showed 44∼67% and 36% inhibition rate against direct mutagen, MNNG (70 ng/assay) induce mutagenicity in the SOS chromotest. Thus GKs delayed fermentation period of kimchi and exhibited higher antimutagenic activity than CK.

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Inhibitory Effect of Methanol Extract of Eleutherococcus senticosus Maxim. on the Direct Mutagen Mutagenicity (직접 돌연변이원에 대한 가시오갈피 추출물의 항돌연변이 효과)

  • 박정섭;안병용;고하영;최동성
    • KSBB Journal
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    • v.18 no.3
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    • pp.217-221
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    • 2003
  • Antimutagenic effects og Eleutherococcus senticosus Maxim. on the mutagenicty induced by mutagens, 4-NQO, MNNG, $\textrm{NaN}_{3}$, 2-NF, and 1-NP was studied by the Ames test with Salmonella typhimurium TA98 and TA100. The methanol extract ($500\mu\textrm{g}$/plate) of E. senticosus Maxim. showed inhibitory effect on the mutagenicty induced by 1-NP only among the tested mutagens. In S. typhimurium TA98, the methanol extracts of the root, stem and leaf showed inhibitory effects of 54.9, 29.5, and 32.9% inhibition on 1-NP mutagenicity, respectively. In S typhimurium TA100, the methanol extracts of the root, stem, and leaf showed inhibitory effects of 593, 30.2, and 43.6%, respectively. The methanol extract were further fractionated by a subsequent liquid-liquid partition technique with chloroform, butanol, and water. The chloroform ($300\mu\textrm{g}$/plate) fraction of the root, stem and leaf showed the strong antimutagenic effects on the mutagenicity induced by 1-NP in S typhimurium TA98 and TA100. But none or weak antimutagenicities were observed in the butanol and aqueous fraction. The chloroform fractions of root, stem and leaf showed the antimutagenic effects of 61.6~88.6% in a dose-dependent manner. In the antimutagenic mode test, the inhibition effect of root was mainly bio-antimutagenic, whereas stem and leaf were desmutagenic.

Antimutagenic Effect of Green-Yellow Vegetables toward Aflatoxin $B_1$, and 4-Nitroquinoline-1-oxide (아플라톡신 $B_1$과 4-NQO에 대한 녹황색 채소류의 항돌연변이 효과)

  • 이경임;박건영;이숙희
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.21 no.2
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    • pp.143-148
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    • 1992
  • The antimutagenic effects of green-yellow vegetables toward aflatoxin B$_1$(AFB$_1$) and 4-nitroquinoline-1-ox-ide (4-NQO) using the Ames assay system with Salmonella typhimurium TA98 and TA100 were studied. Forty six to fifty percent of the methanol extracts of the vegetable samples inhibited the mutagenicity induced by AFB$_1$in TA98 and TA100. Perilla leaf, lettuce, broccoli, crown daisy, water dropwort, small water dropwort, red pepper, red pepper leaves, amaranth, spinach and radish root were significantly reduced the mutagenicity of AFB$_1$(p< 0.01). Whereas 25 out of 27 samples (93%) exhibited antimutagenicity toward a direct mutagen of 4-NQO (p< 0.01. 0.05). The samples which showed the strong antimutagenicity (>60%) were cabbage, kale, lettuce, broccoli, mustard leaf, green red pepper, green sweet pepper, spinach, amaranth, soybean sprout and immature pumpkin. The juices from the several samples also showed antimu-tagenic activity toward AFB$_1$. Cabbage, perilla leaf, small water dropwort and spinach reduced TAT100 revertants dose dependently in the range of 50-500$m\ell$/plate, however, cucumber and carrot showed little effect.

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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.

EFFECTS OF NOVEL DITHIOL MALONATE DERIVATIVES ON LIVER LIPID PEROXIDATION AND ON MICROSOMAL ELECTRON TRANSPORT SYSTEM

  • Park, Keun-Hee;Lee, Jong-Wook
    • Toxicological Research
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    • v.3 no.2
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    • pp.97-110
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    • 1987
  • The effects of 5 novel hepatotrophic agents, dithiol malonate derivatives (DMDs; DMD1-DMD5), on the liver microsomal lipid peroxidation induced by carbon tetrachloride $(CCl_4)$ and the correlations with the changes of microsomal electron transport system were investigated. All DMDs were found to inhibit the lipid peroxidation induced by $CCl_4$ in mice and rats as well in vitro liver microsomal system. Therefore, each DMD seemed to have direct mode of action on liver microsomes to inhibit the lipid peroxidation. As an ex vivo study, the induced lipid peroxidation by $CCl_4$ and the changes in electron transport system were determined with liver microsomes obtained from rats chronically treated with DMDs for 7 days. The induced lipid peroxide contents in liver microsomal system were lower in DMD1, DMD2 and DMD3 treated group, but higher in DMD4 and DMD5 group when compared to the control group. Cyt. p.450 contents in the microsomes were decreased by the treatment with DMD1, DMD2 and DMD3, but increased significantly by DMD4 with great extent and by DMD5 with less extent. The cyt. p-450 isozymes induced by treatment of DMD4 and DMD5 were identified as 3-methylcholanthrene (MC) type. The NADPH cyt. -C reductase activities of the microsomes treated with DMD1, DMD2, DMD4 and DMD5 were increased in the range of around 20% to 50%, but decreased with DMD3, All DMDs increased dyt. $-b_5$ content and did not alter NAdH-cyt, $-b_5$ reductase activities in the microsomes. In summary, the 5 novel hepatotrophic agents (DMDs) markedly protected against lipid peroxidation induced by $CCl_4$ in vivo and in vitro possibly through the mechanism of direct action on the liver microsomes. The degree of inhibition produced by DMDs on lipid peroxidation induced by $CCl_4$ seemed to coincide rather with cyt. p-450 contents than with other components of liver microsomal electron transport system including NADPH-cyt, -C reductase.

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Production of Group Specific Monoclonal Antibody to Aflatoxins and its Application to Enzyme-linked Immunosorbent Assay

  • Kim, Sung-Hee;Cha, Sang-Ho;Karyn, Bischoff;Park, Sung-Won;Son, Seong-Wan;Kang, Hwan-Goo
    • Toxicological Research
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    • v.27 no.2
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    • pp.125-131
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    • 2011
  • Through the present study, we produced a monoclonal antibody against aflatoxin B1 (AFB1) using AFB1-carboxymethoxylamine BSA conjugates. One clone showing high binding ability was selected and it was applied to develop a direct competitive ELISA system. The epitope densities of AFB1-CMO against BSA and KLH were about 1 : 6 and 1 : 545, respectively. The monoclonal antibody (mAb) from cloned hybridoma cell was the IgG1 subclass with ${\lambda}$-type light chains. The $IC_{50}s$ of the monoclonal antibody developed for AFB1, AFB2, AFG1 and AFG2 were 4.36, 7.22, 6.61 and 29.41 ng/ml, respectively, based on the AFB1-KLH coated ELISA system and 15.28, 26.62, 32.75 and 56.67 ng/ml, respectively, based on the mAb coated ELISA. Cross-relativities of mAb to AFB1 for AFB2, AFG1 and AFG2 were 60.47, 65.97 and 14.83% in the AFB1-KLH coated ELISA, and 59.41, 46.66 and 26.97% in the mAb coated ELISA, respectively. Quantitative calculations for AFB1 from the AFB1-Ab ELISA and AFB1-Ag ELISA ranged from 0.25 to 25 ng/ml ($R^2$ > 0.99) and from 1 to 100 ng/ml ($R^2$ > 0.99), respectively. The intra- and inter-assay precision CVs were < 10% in both ELISA assay, representing good reproducibility of developed assay. Recoveries ranged from 79.18 to 91.27%, CVs ranged from 3.21 to 7.97% after spiking AFB1 at concentrations ranging from 5 to 50 ng/ml and following by extraction with 70% methanol solution in the Ab-coated ELISA. In conclusion, we produced a group specific mAb against aflatoxins and developed two direct competitive ELISAs for the detection of AFB1 in feeds based on a monoclonal antibody developed.