• Title/Summary/Keyword: Metabolic activation

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Evaluation of the Genetic Toxicity of Synthetic Chemical (XVII) -In vitro Mouse Lymphoma Assay and In vitro Supravital Micronucleus Assay with 1, 2-Dichlorobenzene

  • Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.2
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    • pp.113-118
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    • 2007
  • Chlorobenzenes due to their acute toxicity and the capability of bioaccumulating are of great health and environmental concern. Especially, 1, 2-dichlorobenzene (CAS No. 95-50-1) is used for organic synthesis, dye manufacture, as a solvent and for other applications in chemical industry. Adverse effects of 1, 2-dichlorobenzene includes increases in liver and kidney weights and hepatotoxicity. In this study, we evaluated the genetic toxicity of 1, 2-dichlorobenzene with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vitro mouse supravital micronucleus (MN) assay. 1, 2-Dichlorobenzene appeared the significantly positive results and the induction of large mutant colonies only in the presence of metabolic activation system with MLA. But in vitro testing of 1, 2-dichlorobenzene yielded negative results with supravital MN assay. These results suggest that 1, 2-dichlorobenzene may play a mutagen rather than clastogen in vitro mammalian system.

Effects of Ginseng Saponin on DNA Strand Breaks and Replication Inhibition by Benzo(a)Pyrene in CHO-Kl Cells (Benzo(a)Pyrene 유발 DNA 상해 및 복제 억제에 미치는 인삼사포닌의 영향)

  • Park, Jin-Kyu;Park, Ki-Hyun
    • Journal of Ginseng Research
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    • v.16 no.3
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    • pp.210-216
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    • 1992
  • The effect of saponin extracted from Panax grneng CA Meyer on DNA repair and replicative DNA synthesis were examined in CHO-Kl cells cotreated with benzo(a)pyrene and rat liver S-15 fraction. The DNA strand breaks inititated by benzo(a)pyrene metabolites were measured by alkaline election technique. The addition of ginseng saponin to the culture media resulted in decrease of benzo(a)pyrene-induced DNA strand breaks, and restored the suppressed-semiconservative-DNA-synthesis by the carcinogen. DNA repair synthesis in the damaged cells was also elevated by the ginseng treatment when the repairing activites were measured for the (3H)-thymidine incorporation into the carcinogen damaged cellular DNk Comparative analysis of DNA-adduces of benzo(a)pyrene metabortes in microsomes suggested that ginseng saponin treatment in rats reduced the formation of electrophilic metabolites of benzo (a)-pyrene in the rat liver microsomes.

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Bacterial Reverse Mutation Test of 1,2,4-trimethylbenzene (1,2,4-trimethylbenzene의 미생물복귀돌연변이시험)

  • Kim, Soo-Jin;Cho, Hae-Won;Rim, Kyung-Taek;Maeng, Seung-Hee;Kim, Hyeon-Yeong
    • Environmental Analysis Health and Toxicology
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    • v.21 no.4 s.55
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    • pp.317-322
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    • 2006
  • We have investigated the genotoxicity of 1,2,4-trimethylbenzene using Ames reverse mutation test. In Ames reverse mutation test, 1,2,4-trimethylbenzene treatment at the dose of 100, 50, 25, 12.5, $6.25{\mu}g/plate$ did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and in Escherichia coli WP2uvrA with and without metabolic activation. These results indicate that 1,2,4-trimethylbenzene has no mutagenic potential under the rendition in this study.

Ginseng Prevents DNA-adduct Formation in Rat Hepatocytes in vitro Treated with DMBA

  • Kumar, Ashok
    • Proceedings of the Ginseng society Conference
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    • 1998.06a
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    • pp.263-269
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    • 1998
  • It is an established fact that most of the carcinogens implicate bay-region diol epoxides as the ultimate carcinogenic metabolites. These electrophiles react with nucleophilic sites in the cells to form abducts. It is the formation of carcinogenic-DNA adducts that is thought to initiate carcinogenesis. In our previous study we have reported chemopreventive property of Ginseng on 7,12-dimethylbenz (a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. In this study we have examined the effect on formation of DMBA-DNA adducts in rat hepatocytes pretreated with ginseng. Primary cultures of rat hepatocytes were used. The cells wets treated with ginseng for 24 hrs and then with DMBA (iOn) for 18 hrs. Cells were then harvested, their DNA was isolated and analyzed by P)2 labelling. A significant reduction in the levels of DMBA-DNA adduces (adducts/108 nucleotides) was observed in all cultures pretreated with ginseng. The viability of cells was not affected by pre-treatment with ginseng. Our finding suggests that ginseng block or suppresses the events associated with chemical carcinogenesis by inhibiting metabolic activation of the carcinogens.

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A STUDY ON THE CLASTOGENICITY OF TRICHOTHECENE MYCOTOXINS IN CHINESE HAMSTER LUNG CELLS

  • Ryu, Jae-Chun;Chang, Il-Moo
    • Toxicological Research
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    • v.9 no.1
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    • pp.13-21
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    • 1993
  • The chromosomal aberration of the trichothecene mycotoxins such as T-2 toxin (T-2), HT-2 toxin (HT-2), nivalenol (NIV) and deoxynivalenol (DON) which are one of the most important food borne contaminants produced by Fusarium species fungi, was investigated in the chinese hamster lung cells. These trichothecene mycotoxins showed high cytotoxicity in order of T-2, HT-2, NIV, and DON to the chinese hamster lung cells. Nevertheless high cytotoxicity of these trichothecene mycotoxins, no clastogenicity of T-2 and HT-2 in the range of 0.01-0.0025 ng/ml, of NIV in that of 0.3-0.075ng/ml, and of DON in that of 1.0-0.25 ng/ml was observed in both with and without metabolic activation system.

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Mutagenicity Study of (R)-JG-381, A New Antidiabetic Agent (항당뇨물질 (R)-JG-381의 변이원성 시험)

  • 오우용;주상섭;박형근;함광수;조장섭;이선미
    • Biomolecules & Therapeutics
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    • v.8 no.3
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    • pp.248-254
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    • 2000
  • (R)-JG-381, a R form of alkylglycidic acid derivative, was examined for mutagenicity in the reverse mutation test on bacteria, chromosomal aberration test on cultured mammalian cells and micronucleus test in mice. In the reverse mutation test on bacteria using Salmonella typhimurium strain TA98, TA100, TA102, TA1535, TA1537 with or without a metabolic activation system (S9 mix), (R)-JG-381 did not affect the revertant colonies but significantly increased revertant colonies in one test strain, TA98, compared with the vehicle control. In the chromosomal aberration (CA) test using cultured Chinese Hamster Lung fibroblast(CHL) cells, the number of aberrant cells was clot increased in the presence or absence of 59 mix at concentration of the (R)-JG-381 0.025 $\mu$l/m1 to 0.1 $\mu$l/m1, compared with vehicle control. In the micronucleus (MN) test, micronucleated polychromatic erythrocytes in the (R)-JG-381-treated mice were not different from those of the vehicle-treated mice.

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Mutagenicity of Chinese Herbal Anti-cancer Drugs and Their Antimutagenic Activity to Base-pair Substitution Mutagen (치암중초약의 돌연변이유발 및 돌연변이유발 억제효과)

  • Lee, Hyun-Chul
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.185-193
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    • 1987
  • Ten species of herbae, which have been used to treat cancers in Chinese medicine, were tested to investigate their mutagenicity or antimutagenicity in S. typhimurium TA97, TA98, TA100, TA1535, and TA1538. Scolopendra centipede was weakly active in reversion of the frameshift mutation in S. typhimurium TA97 strain and the base-pair substitution in TA100 and TA1535 strains. Other herbae such as Coix lachryma, Dianthus superbus, Tricanthoshse kirilowii, Eupatorium formosanum, Lithospermum erythrorhizon, Ansaema japonicum, Curcuma zedoaria, Helicteres angustifolia, and Euonymus sieboldianus did not show any of the mutagenic potential, regardless of the metabolic activation with rat hepatic microsomal fraction. Dianthus superbus, Eupatorium formosanum, and Euonymus sieboldianus exhibited suppressive activities on microbial mutagenesis of N-methyl-N'-nitrosoguanidine, a base-pair substitution mutagen, in TA1535 and TA100 tester strains. The antimutagenic activities of Dianthus superbus and Euonymus sieboldianus appeared to be dose-dependant.

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Genetic Effects of Pesticides in the Mammalian Cells: I. Induction of Micronucleus

  • Park, Sang-Gi;Lee, Se-Yong
    • The Korean Journal of Zoology
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    • v.20 no.1
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    • pp.19-28
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    • 1977
  • In order to evaluate the mutagenic potential in animal for these pesticides which were proved to be mutagenic in the bacterial screening system with a metabolic activation in vitro, we have studied in vivo cytogenetic effects on mouse bone marrow by means of the micronucleus test. The clastogenic activity of the chemical is evaluated as the frequency of micronuclei in polychromatic erythrocytes. We have tested six pesticides, insecticides, DDVP and trichlorfon, fungicide, TMTD, herbicides, NIP and MO and growth regula색, maleic hydrazide. It was found that among the tested pesticides only TMTD exhibited minimal activity in inducing micronuclei. Organophosphorus insecticide DDVP that is the most broadly used and economically important chemical, did not increase the micronuclei frequencies in mouse bone marrow cells as with the all other pesticides tested.

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Induction of Apoptosis by N-nitrosocarbofuran, via Cytochrome c-Mediated Activation of Caspase-3 protease

  • Lee, Bang-Wool;Oh, Seon-Hee;Lee, Byung-Hoon
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.158.1-158.1
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    • 2003
  • Carbofuran(CF) is one of the most widely used carbamate pesticides in the world applied for insect and nematode control. Due to its widespread use in agriculture and households, contamination of food, water, and air has become serious, and consequently adverse health effects are inevitable in humans, animals, wildlife and fish, it has reported that CF alone or in combination with other carbamate insecticides influences the level of reproductive and metabolic hormones such as thyroxine and corticosterone, and results in impairment of endocrine, immune behavioral functions. (omitted)

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Role of metabolism by flavin-containing monooxygenase in thioacetamide-induced immunosuppression

  • Lee, Jeong W.;Ki D. Shin;Shin W. Cha;Kim, Jong-C.;Kim, Eun J.;Sang S. Han;Tae C. Jeong;Woo S. Koh
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.121-121
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    • 2001
  • Thioacetamide has been known to cause immune suppression. In this report we studied the role of metabolic activation by flavin-containing monooxygenase in the thioacetamide-induced immune response. To determine whether the metabolites of thioacetamide produced by flavin-containing monooxygenase result in the immunosuppression, methimazole, a flavin-containing monooxygenase inhibitor, was used to block the flavin-containing monooxygenase pathway.(omitted)

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